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Cognitive impairment

MedGen UID:
383844
Concept ID:
C1856145
Finding
Synonyms: Abnormality of cognition; Cognitive abnormality; Cognitive defects; Cognitive deficits; Intellectual impairment; Mental impairment
 
HPO: HP:0100543

Conditions with this feature

Acrocephalosyndactyly type I
MedGen UID:
7858
Concept ID:
C0001193
Congenital Abnormality
The eight disorders comprising the FGFR-related craniosynostosis spectrum are Pfeiffer syndrome, Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, FGFR2-related isolated coronal synostosis, Jackson-Weiss syndrome, Crouzon syndrome with acanthosis nigricans (AN), and Muenke syndrome (isolated coronal synostosis caused by the p.Pro250Arg mutation in FGFR3). Muenke syndrome and FGFR2-related isolated coronal synostosis are characterized only by uni- or bicoronal craniosynostosis; the remainder are characterized by bicoronal craniosynostosis or cloverleaf skull, distinctive facial features, and variable hand and foot findings.
alpha Thalassemia
MedGen UID:
1434
Concept ID:
C0002312
Disease or Syndrome
Alpha-thalassemia (a-thalassemia) has two clinically significant forms: hemoglobin Bart hydrops fetalis (Hb Bart) syndrome and hemoglobin H (HbH) disease. Hb Bart syndrome, the more severe form, is characterized by fetal onset of generalized edema, pleural and pericardial effusions, and severe hypochromic anemia, in the absence of ABO or Rh blood group incompatibility. Clinical features include: hepatosplenomegaly, extramedullary erythropoiesis, hydrocephaly, and cardiac and urogenital defects. Death usually occurs in the neonatal period. HbH disease is characterized by microcytic hypochromic hemolytic anemia, hepatosplenomegaly, mild jaundice, and sometimes thalassemia-like bone changes. Carriers of aº-thalassemia (a-thalassemia trait) show microcytosis, hypochromia, and normal percentages of HbA2 and HbF. Carriers of a(+)-thalassemia (a-thalassemia silent carrier) have either a silent hematologic phenotype or present with a moderate thalassemia-like hematologic picture. Homozygosity for a(+)-thalassemia results in an aº-thalassemia (a-thalassemia trait) hematologic phenotype.
Fabry's disease
MedGen UID:
8083
Concept ID:
C0002986
Disease or Syndrome
Fabry disease results from deficient activity of the enzyme a-galactosidase (a-Gal A) and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The classic form, occurring in males with less than 1% a-Gal A enzyme activity, usually has its onset in childhood or adolescence with periodic crises of severe pain in the extremities (acroparesthesias), the appearance of vascular cutaneous lesions (angiokeratomas), sweating abnormalities (anhydrosis, hypohydosis, and rarely hyperhidrosis), characteristic corneal and lenticular opacities, and proteinuria. Gradual deterioration of renal function to end-stage renal disease (ESRD) usually occurs in men in the third to fifth decade. In middle age, most males successfully treated for ESRD develop cardiac and/or cerebrovascular disease, a major cause of morbidity and mortality. Heterozygous females typically have milder symptoms at a later age of onset than males. Rarely, they may be relatively asymptomatic throughout a normal life span or may have symptoms as severe as those observed in males with the classic phenotype. In contrast, males with greater than 1% a-Gal A activity may have either (1) a cardiac variant phenotype that usually presents in the sixth to eighth decade with left ventricular hypertrophy, mitral insufficiency and/or cardiomyopathy, and proteinuria, but without ESRD; or (2) a renal variant phenotype, associated with ESRD but without the skin lesions or pain.
Gorlin syndrome
MedGen UID:
2554
Concept ID:
C0004779
Neoplastic Process
Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple jaw keratocysts, frequently beginning in the second decade of life, and/or basal cell carcinomas (BCCs) usually from the third decade onward. Approximately 60% of individuals have a recognizable appearance with macrocephaly, bossing of the forehead, coarse facial features, and facial milia. Most individuals have skeletal anomalies (e.g., bifid ribs, wedge-shaped vertebrae). Ectopic calcification, particularly in the falx, is present in more than 90% of affected individuals by age 20 years. Cardiac and ovarian fibromas occur in approximately 2% and 20% of individuals respectively. Approximately 5% of children with NBCCS develop medulloblastoma (primitive neuroectodermal tumor [PNET]), generally the desmoplastic subtype. Peak incidence is at age two years. Life expectancy in NBCCS is not significantly different from average.
Bloom syndrome
MedGen UID:
2685
Concept ID:
C0005859
Congenital Abnormality
Bloom’s syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, highly characteristic sparseness of subcutaneous fat tissue throughout infancy and early childhood, and short stature throughout postnatal life that in most affected individuals is accompanied by an erythematous and sun-sensitive skin lesion of the face. Gastroesophageal reflux (GER) is common and very possibly responsible for infections of the upper respiratory tract, the middle ear, and the lung that occur repeatedly in most persons with BSyn. Although most affected individuals have normal intellectual ability, many exhibit a poorly defined (and little studied) learning disability. Women may be fertile, but menopause occurs unusually early; men are infertile. Serious medical complications that are much more common than in the general population and that also appear at unusually early ages are chronic obstructive pulmonary disease, diabetes mellitus resembling the adult-onset type, and cancer of a wide variety of types and anatomic sites. BSyn is very rare in all national and ethnic groups but is relatively less rare in Ashkenazi Jews.
Chédiak-Higashi syndrome
MedGen UID:
3347
Concept ID:
C0007965
Disease or Syndrome
Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism (OCA), immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, a lymphoproliferative infiltration of the bone marrow and reticuloendothelial system. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Premature closure of one or more CRANIAL SUTURES. It often results in plagiocephaly. Craniosynostoses that involve multiple sutures are sometimes associated with congenital syndromes such as ACROCEPHALOSYNDACTYLIA; and CRANIOFACIAL DYSOSTOSIS.
5p partial monosomy syndrome
MedGen UID:
41345
Concept ID:
C0010314
Congenital Abnormality
Cri-du-chat syndrome was first described by Lejeune et al. (1963) as a hereditary congenital syndrome associated with deletion of part of the short arm of chromosome 5. The deletions can vary in size from extremely small and involving only band 5p15.2 to the entire short arm. Although the majority of deletions arise as new mutations, approximately 12% result from unbalanced segregation of translocations or recombination involving a pericentric inversion in one of the parents.
Chondroectodermal dysplasia
MedGen UID:
8584
Concept ID:
C0013903
Disease or Syndrome
Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals (summary by Ruiz-Perez et al., 2000). The clinical features of the Ellis-van Creveld syndrome appear to be identical regardless of whether the disorder is caused by mutation in the EVC gene (604831) or in the EVC2 gene (607261) (Ruiz-Perez et al., 2003, Galdzicka et al., 2002).
Endocardial fibroelastosis
MedGen UID:
4041
Concept ID:
C0014117
Disease or Syndrome
A condition characterized by the thickening of ENDOCARDIUM due to proliferation of fibrous and elastic tissue, usually in the left ventricle leading to impaired cardiac function (CARDIOMYOPATHY, RESTRICTIVE). It is most commonly seen in young children and rarely in adults. It is often associated with congenital heart anomalies (HEART DEFECTS CONGENITAL;) INFECTION; or gene mutation. Defects in the tafazzin protein, encoded by TAZ gene, result in a form of autosomal dominant familial endocardial fibroelastosis.
Progressive myositis ossificans
MedGen UID:
4698
Concept ID:
C0016037
Disease or Syndrome
Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner, with most patients being confined to a wheelchair by the third decade of life and requiring lifelong care (summary by Petrie et al., 2009).
Focal dermal hypoplasia
MedGen UID:
42055
Concept ID:
C0016395
Disease or Syndrome
Focal dermal hypoplasia is a multisystem disorder characterized primarily by involvement of the skin, skeletal system, eyes, and face. Skin manifestations present at birth include atrophic and hypoplastic areas of skin; cutis aplasia; fat nodules in the dermis manifesting as soft, yellow-pink cutaneous nodules; and pigmentary changes. Verrucoid papillomas of the skin and mucous membranes may appear later. The nails can be ridged, dysplastic, or hypoplastic; hair can be sparse or absent. Limb malformations include oligo/syndactyly and split hand/foot. Developmental abnormalities of the eye can include anophthalmia/microphthalmia, iris and chorioretinal coloboma, and lacrimal duct abnormalities. Craniofacial findings can include facial asymmetry, notched alae nasi, cleft lip and palate, and pointed chin. Occasional findings include dental anomalies, abdominal wall defects, diaphragmatic hernia, and renal anomalies. Psychomotor development is usually normal; some individuals have cognitive impairment.
Fragile X syndrome
MedGen UID:
8912
Concept ID:
C0016667
Disease or Syndrome
FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related primary ovarian insufficiency (POI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function mutation and is nearly always characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Because FMR1 mutations are complex alterations involving non-classic gene-disrupting alterations (trinucleotide repeat expansion) and abnormal gene methylation, affected individuals occasionally have an atypical presentation with an IQ above 70, the traditional demarcation denoting intellectual disability (previously referred to as mental retardation). Males with an FMR1 full mutation accompanied by aberrant methylation may have a characteristic appearance (large head, long face, prominent forehead and chin, protruding ears), connective tissue findings (joint laxity), and large testes after puberty. Behavioral abnormalities, sometimes including autism spectrum disorder, are common. FXTAS occurs in males (and some females) who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor. FMR1-related POI (age at cessation of menses <40 years) occurs in approximately 20% of females who have an FMR1 premutation.
Fucosidosis
MedGen UID:
5288
Concept ID:
C0016788
Disease or Syndrome
Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Fucosidosis has been classified into 2 major types. Type 1 is characterized by rapid psychomotor regression and severe neurologic deterioration beginning at about 6 months of age, elevated sweat sodium chloride, and death within the first decade of life. Type 2 is characterized by milder psychomotor retardation and neurologic signs, the development of angiokeratoma corporis diffusum, normal sweat salinity, and longer survival (Kousseff et al., 1976).
Glycogen storage disease, type II
MedGen UID:
5340
Concept ID:
C0017921
Disease or Syndrome
Glycogen storage disease type II (GSD II), or Pompe disease, is classified by age of onset, organ involvement, severity, and rate of progression. Classic infantile-onset Pompe disease may be apparent in utero but more often presents in the first two months of life with hypotonia, generalized muscle weakness, cardiomegaly and hypertrophic cardiomyopathy, feeding difficulties, failure to thrive, respiratory distress, and hearing loss. Without treatment by enzyme replacement therapy (ERT), classic infantile-onset Pompe disease commonly results in death in the first year of life from progressive left ventricular outflow obstruction. The non-classic variant of infantile-onset Pompe disease usually presents within the first year of life with motor delays and/or slowly progressive muscle weakness, typically resulting in death from ventilatory failure in early childhood. Cardiomegaly can be seen, but heart disease is not a major source of morbidity. Late-onset (i.e., childhood, juvenile, and adult-onset) Pompe disease is characterized by proximal muscle weakness and respiratory insufficiency; clinically significant cardiac involvement is uncommon in the late-onset form.
Glycogen storage disease type III
MedGen UID:
6641
Concept ID:
C0017922
Disease or Syndrome
Glycogen storage disease type III (GSD III) is characterized by variable liver, cardiac muscle, and skeletal muscle involvement. GSD IIIa, the most common subtype present in about 85% of affected individuals, manifests with liver and muscle involvement; GSD IIIb, with liver involvement only, comprises about 15% of all GSD III. In infancy and early childhood, liver involvement presents as ketotic hypoglycemia, hepatomegaly, hyperlipidemia, and elevated hepatic transaminases. In adolescence and adulthood, liver disease becomes less prominent. Hypertrophic cardiomyopathy develops in the majority of those with GSD IIIa, usually during childhood. Its clinical significance ranges from asymptomatic in the majority to severe cardiac dysfunction, congestive heart failure, and rarely sudden death. Skeletal myopathy manifesting as weakness is not usually evident in childhood, but slowly progresses, typically becoming prominent in the third to fourth decade.
Hallermann-Streiff syndrome
MedGen UID:
5414
Concept ID:
C0018522
Congenital Abnormality
Hallermann-Streiff syndrome is characterized by a typical skull shape (brachycephaly with frontal bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, skin atrophy, dental anomalies, and proportionate short stature (Hallermann, 1948; Streiff, 1950; Francois, 1958). Mental retardation is present in a minority of cases (Gorlin et al., 1990).
Cowden syndrome
MedGen UID:
5420
Concept ID:
C0018553
Neoplastic Process
Cowden syndrome is a disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers. Almost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties. Cowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include colorectal cancer, kidney cancer, and a form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development or intellectual disability. The features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors. Both conditions can be caused by mutations in the PTEN gene. Some people with Cowden syndrome have had relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions. Some people have some of the characteristic features of Cowden syndrome, particularly the cancers associated with this condition, but do not meet the strict criteria for a diagnosis of Cowden syndrome. These individuals are often described as having Cowden-like syndrome.
Neutral 1 amino acid transport defect
MedGen UID:
6723
Concept ID:
C0018609
Disease or Syndrome
An autosomal recessive inherited metabolic disorder caused by mutations in the SLC6A19 gene. It is characterized by defective absorption of neutral amino acids. Signs and symptoms include skin eruptions reminiscent of pellagra, aminoaciduria, and cerebellar ataxia.
Hereditary insensitivity to pain with anhidrosis
MedGen UID:
6915
Concept ID:
C0020074
Disease or Syndrome
Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.
Incontinentia pigmenti syndrome
MedGen UID:
7049
Concept ID:
C0021171
Disease or Syndrome
Incontinentia pigmenti (IP) is a disorder that affects the skin, hair, teeth, nails, eyes, and central nervous system. Characteristic skin lesions evolve through four stages: I. Blistering (birth to age ~4 months). II. Wart-like rash (for several months). III. Swirling macular hyperpigmentation (age ~6 months into adulthood) . IV. Linear hypopigmentation. Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Neovascularization of the retina, present in some individuals, predisposes to retinal detachment. Neurologic findings including cognitive delays/intellectual disability and learning disability are occasionally seen.
Hypomelanosis of Ito
MedGen UID:
5920
Concept ID:
C0022283
Disease or Syndrome
A neurocutaneous syndrome characterized by a bizarre, more or less symmetrical leukoderma with depigmented streaks, patches, and whorls, sometimes associated with hyperkeratosis follicularis. Associated disorders include seizures, psychomotor retardation, macrocephaly, and ophthalmological and other abnormalities.
Menkes kinky-hair syndrome
MedGen UID:
44030
Concept ID:
C0022716
Disease or Syndrome
Menkes disease, occipital horn syndrome (OHS), and ATP7A-related distal motor neuropathy (DMN) are disorders of copper transport caused by mutations in the copper-transporting ATPase gene (ATP7A). Infants with classic Menkes disease appear healthy until age two to three months, when loss of developmental milestones, hypotonia, seizures, and failure to thrive occur. The diagnosis is usually suspected when infants exhibit typical neurologic changes and concomitant characteristic changes of the hair (short, sparse, coarse, twisted, and often lightly pigmented). Temperature instability and hypoglycemia may be present in the neonatal period. Death usually occurs by age three years. Occipital horn syndrome is characterized by "occipital horns," distinctive wedge-shaped calcifications at the sites of attachment of the trapezius muscle and the sternocleidomastoid muscle to the occipital bone. Occipital horns may be clinically palpable or observed on skull radiographs. Individuals with OHS also have lax skin and joints, bladder diverticula, inguinal hernias, and vascular tortuosity. Intellect is normal or slightly reduced. ATP7A-related distal motor neuropathy, an adult-onset disorder resembling Charcot-Marie-Tooth disease, shares none of the clinical or biochemical abnormalities characteristic of Menkes disease or OHS.
Klippel Trenaunay syndrome
MedGen UID:
9646
Concept ID:
C0022739
Congenital Abnormality
Klippel-Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues, and bones. The disorder has three characteristic features: a red birthmark called a port-wine stain, abnormal overgrowth of soft tissues and bones, and vein malformations. Most people with Klippel-Trenaunay syndrome are born with a port-wine stain. This type of birthmark is caused by swelling of small blood vessels near the surface of the skin. Port-wine stains are typically flat and can vary from pale pink to deep maroon in color. In people with Klippel-Trenaunay syndrome, the port-wine stain usually covers part of one limb. The affected area may become lighter or darker with age. Occasionally, port-wine stains develop small red blisters that break open and bleed easily. Klippel-Trenaunay syndrome is also associated with overgrowth of bones and soft tissues beginning in infancy. Usually this abnormal growth is limited to one limb, most often one leg. However, overgrowth can also affect the arms or, rarely, the trunk. The abnormal growth can cause pain, a feeling of heaviness, and reduced movement in the affected area. If the overgrowth causes one leg to be longer than the other, it can also lead to problems with walking. Malformations of veins are the third major feature of Klippel-Trenaunay syndrome. These abnormalities include varicose veins, which are swollen and twisted veins near the surface of the skin that often cause pain. Varicose veins usually occur on the sides of the upper legs and calves. Veins deep in the limbs can also be abnormal in people with Klippel-Trenaunay syndrome. Malformations of deep veins increase the risk of a type of clot called a deep vein thrombosis (DVT). If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE). Complications of Klippel-Trenaunay syndrome can include a type of skin infection called cellulitis, swelling caused by a buildup of fluid (lymphedema), and internal bleeding from abnormal blood vessels. Less commonly, this condition is also associated with fusion of certain fingers or toes (syndactyly) or the presence of extra digits (polydactyly).
Langer-Giedion syndrome
MedGen UID:
6009
Concept ID:
C0023003
Disease or Syndrome
Langer-Giedion syndrome is a condition that causes bone abnormalities and distinctive facial features. People with this condition have multiple noncancerous (benign) bone tumors called exostoses. Multiple exostoses may result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the exostoses. Affected individuals also have short stature and cone-shaped ends of the long bones (epiphyses). The characteristic appearance of individuals with Langer-Giedion syndrome includes sparse scalp hair, a rounded nose, a long flat area between the nose and the upper lip (philtrum), and a thin upper lip. Some people with this condition have loose skin in childhood, which typically resolves with age. Affected individuals may have some intellectual disability.
Laurence-Moon syndrome
MedGen UID:
44078
Concept ID:
C0023138
Disease or Syndrome
Laurence-Moon syndrome has a clinical presentation similar to that of Oliver-McFarlane syndrome (275400), including chorioretinopathy and pituitary dysfunction, but with childhood onset of ataxia, peripheral neuropathy, and spastic paraplegia and without trichomegaly. Historically, Laurence-Moon syndrome has been associated with Bardet-Biedl syndrome (see BBS, 209900) (summary by Hufnagel et al., 2015). Oliver-McFarlane syndrome is an allelic disorder.
Deficiency of alpha-mannosidase
MedGen UID:
7467
Concept ID:
C0024748
Disease or Syndrome
Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. Three clinical subtypes include: A mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression (type 1); A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression (type 2); and A severe form manifested as prenatal loss or early death from progressive central nervous system involvement (type 3). Individuals with a milder phenotype have mild-to-moderate intellectual disability, impaired hearing, characteristic coarse features, clinical or radiographic skeletal abnormalities, immunodeficiency, and primary central nervous system disease, mainly cerebellar involvement causing ataxia. Periods of psychiatric symptoms are common. Associated medical problems can include corneal opacities, hepatosplenomegaly, aseptic destructive arthritis, and metabolic myopathy. Alpha-mannosidosis is insidiously progressive; some individuals may live into the sixth decade.
Marinesco-Sjögren syndrome
MedGen UID:
6222
Concept ID:
C0024814
Disease or Syndrome
Marinesco-Sjögren syndrome (MSS) is characterized by cerebellar ataxia with cerebellar atrophy, early-onset (not necessarily congenital) cataracts, mild to severe intellectual disability, hypotonia, and muscle weakness. Additional features are short stature and various skeletal abnormalities including scoliosis. Children with MSS usually present with muscular hypotonia in early infancy; distal and proximal muscular weakness is noticed during the first decade of life. Later, cerebellar findings of truncal ataxia, dysdiadochokinesia, and dysarthria become apparent. Motor function worsens progressively for some years, then stabilizes at an unpredictable age and degree of severity. Cataracts can develop rapidly and typically require lens extraction in the first decade of life. Although many adults are severely handicapped, life span in MSS appears to be near normal.
Mohr syndrome
MedGen UID:
10077
Concept ID:
C0026363
Disease or Syndrome
Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes). Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder. The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability. Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums. Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism). Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome. Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.
Mucopolysaccharidosis, MPS-II
MedGen UID:
7734
Concept ID:
C0026705
Disease or Syndrome
Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycans (GAG) accumulation. The vast majority of affected individuals are male; on rare occasion heterozygous females manifest findings. Age of onset, disease severity, and rate of progression vary significantly among affected males. In those with early progressive disease, CNS involvement (manifest primarily by progressive cognitive deterioration), progressive airway disease, and cardiac disease usually result in death in the first or second decade of life. In those with slowly progressive disease, the CNS is not (or is minimally) affected, although the effect of GAG accumulation on other organ systems may be early progressive to the same degree as in those who have progressive cognitive decline. Survival into the early adult years with normal intelligence is common in the slowly progressing form of the disease. Additional findings in both forms of MPS II include: short stature; macrocephaly with or without communicating hydrocephalus; macroglossia; hoarse voice; conductive and sensorineural hearing loss; hepato-splenomegaly; dysostosis multiplex; spinal stenosis; and carpal tunnel syndrome.
Mucopolysaccharidosis type VI
MedGen UID:
44514
Concept ID:
C0026709
Disease or Syndrome
Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism. Intelligence is usually normal (Azevedo et al., 2004).
Steinert myotonic dystrophy syndrome
MedGen UID:
10239
Concept ID:
C0027126
Disease or Syndrome
Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. The clinical findings, which span a continuum from mild to severe, have been categorized into three somewhat overlapping phenotypes: mild, classic, and congenital. Mild DM1 is characterized by cataract and mild myotonia (sustained muscle contraction); life span is normal. Classic DM1 is characterized by muscle weakness and wasting, myotonia, cataract, and often cardiac conduction abnormalities; adults may become physically disabled and may have a shortened life span. Congenital DM1 is characterized by hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common.
Lowe syndrome
MedGen UID:
18145
Concept ID:
C0028860
Disease or Syndrome
Lowe syndrome (oculocerebrorenal syndrome) is characterized by involvement of the eyes, central nervous system, and kidneys. Dense congenital cataracts are found in all affected boys and infantile glaucoma in approximately 50%. All boys have impaired vision; corrected acuity is rarely better than 20/100. Generalized hypotonia is noted at birth and is of central (brain) origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but normal motor tone and strength are never achieved. Motor milestones are delayed. Almost all affected males have some degree of intellectual disability; 10%-25% function in the low-normal or borderline range, approximately 25% in the mild-to-moderate range, and 50%-65% in the severe-to-profound range of intellectual disability. Affected males have varying degrees of proximal renal tubular dysfunction of the Fanconi type, including bicarbonate wasting and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, aminoaciduria, low molecular-weight (LMW) proteinuria, sodium and potassium wasting, and polyuria. Fanconi syndrome is usually not clinically apparent in the first few months of life, but symptoms may appear by age six to 12 months. Glomerulosclerosis associated with chronic tubular injury usually results in slowly progressive chronic renal failure and end-stage renal disease after age ten to 20 years.
Acrocephaly
MedGen UID:
10522
Concept ID:
C0030044
Congenital Abnormality
Premature closing of the lambdoid and coronal sutures.
Phenylketonuria
MedGen UID:
19244
Concept ID:
C0031485
Disease or Syndrome
Phenylalanine hydroxylase (PAH) deficiency results in intolerance to the dietary intake of the essential amino acid phenylalanine and produces a spectrum of disorders including phenylketonuria (PKU), non-PKU hyperphenylalaninemia (non-PKU HPA), and variant PKU. Classic PKU is caused by a complete or near-complete deficiency of phenylalanine hydroxylase activity; without dietary restriction of phenylalanine, most children with PKU develop profound and irreversible intellectual disability. Non-PKU HPA is associated with a much lower risk of impaired cognitive development in the absence of treatment.
Rothmund-Thomson syndrome
MedGen UID:
10819
Concept ID:
C0032339
Disease or Syndrome
Rothmund-Thomson syndrome (RTS) is characterized by poikiloderma; sparse hair, eyelashes, and/or eyebrows; small stature; skeletal and dental abnormalities; cataracts; and an increased risk for cancer, especially osteosarcoma. The skin is typically normal at birth; the rash of RTS develops between age three and six months as erythema, swelling, and blistering on the face and subsequently spreads to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, punctate atrophy, and telangiectases, collectively known as poikiloderma. Hyperkeratotic lesions occur in approximately one third of individuals. Skeletal abnormalities include dysplasias, absent or malformed bones (such as absent radii), osteopenia, and delayed bone formation.
Prune belly syndrome
MedGen UID:
18718
Concept ID:
C0033770
Congenital Abnormality
In its rare complete form, 'prune belly' syndrome comprises megacystis (massively enlarged bladder) with disorganized detrusor muscle, cryptorchidism, and thin abdominal musculature with overlying lax skin (summary by Weber et al., 2011).
Pseudohypoparathyroidism type 1A
MedGen UID:
46178
Concept ID:
C0033806
Disease or Syndrome
Pseudohypoparathyroidism is a term applied to a heterogeneous group of disorders whose common feature is end-organ resistance to parathyroid hormone (PTH; 168450). In addition to PTH resistance, PHP Ia is characterized by resistance to other hormones, including thyroid-stimulating hormone (TSH; see TSHB, 188540) and gonadotropins. PHP Ia is associated with a constellation of clinical features referred to as Albright hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation (Mantovani and Spada, 2006). In contrast, pseudopseudohypoparathyroidism (PPHP; 612463) is characterized by the physical findings of AHO but without hormone resistance (Kinard et al., 1979; Fitch, 1982; Mantovani and Spada, 2006). PHP1A occurs only after maternal inheritance of the molecular defect, whereas PPHP occurs only after paternal inheritance of the molecular defect (Davies and Hughes, 1993; Wilson et al., 1994). This is an example of imprinting, with differential gene expression depending on the parent of origin of the allele. See INHERITANCE and PATHOGENESIS sections.
Pseudopseudohypoparathyroidism
MedGen UID:
10995
Concept ID:
C0033835
Disease or Syndrome
Patients with pseudopseudohypoparathyroidism do not show resistance to parathyroid hormone (PTH; 168450) or other hormones, as is the case with PHP1A (103580), but do manifest the constellation of clinical features referred to as Albright hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation (Kinard et al., 1979; Fitch, 1982; Mantovani and Spada, 2006). PPHP occurs only after paternal inheritance of the molecular defect, whereas PHP1A occurs only after maternal inheritance of the molecular defect (see Inheritance and Pathogenesis below). This is an example of imprinting, with differential gene expression depending on the parent of origin of the allele (Davies and Hughes, 1993; Wilson et al., 1994). For a general phenotypic description, classification, and a discussion of molecular genetics of pseudohypoparathyroidism, see PHP1A (103580).
Sandhoff disease
MedGen UID:
11313
Concept ID:
C0036161
Disease or Syndrome
Sandhoff disease is a progressive neurodegenerative disorder characterized by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease (272800).
Schwartz Jampel syndrome type 1
MedGen UID:
19892
Concept ID:
C0036391
Congenital Abnormality
A syndrome of short stature; generalized myotonia with contractures of major joints, microstomia, and muscle rigidity; ocular anomalies, mainly blepharophimosis; and characteristic facies marked by pinched or frozen smile puckered lips. Some degree of mental retardation occurs in about 25% of patients. The affected children usually appear normal at birth and the symptoms become recognizable at 1 to 3 years of age. Malignant hyperthermia is a potentially lethal hazard during anesthesia.
Shy-Drager syndrome
MedGen UID:
20740
Concept ID:
C0037019
Disease or Syndrome
Multiple system atrophy (MSA) is a distinct clinicopathologic entity that manifests as a progressive adult-onset neurodegenerative disorder causing parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Two main subtypes are recognized: 'subtype C,' characterized predominantly by cerebellar ataxia, and 'subtype P,' characterized predominantly by parkinsonism. MSA is characterized pathologically by the degeneration of striatonigral and olivopontocerebellar structures and glial cytoplasmic inclusions that consist of abnormally phosphorylated alpha-synuclein (SNCA; 163890) or tau (MAPT; 157140) (Gilman et al., 1998; Gilman et al., 2008; Scholz et al., 2009). 'Subtype C' of MSA has been reported to be more prevalent than 'subtype P' in the Japanese population (65-67% vs 33-35%), whereas 'subtype P' has been reported to be more prevalent than 'subtype C' in Europe (63% vs 34%) and North America (60% vs 13%, with 27% of cases unclassified) (summary by the The Multiple-System Atrophy Research Collaboration, 2013). MSA is similar clinically and pathologically to Parkinson disease (PD; 168600) and Lewy body dementia (127750). See also PARK1 (168601), which is specifically caused by mutation in the SNCA gene. Pure autonomic failure manifests as orthostatic hypotension and other autonomic abnormalities without other neurologic involvement. Although there is some phenotypic overlap, the relationship of pure autonomic failure to MSA is unclear (Vanderhaeghen et al., 1970; Schatz, 1996).
Sjögren-Larsson syndrome
MedGen UID:
11443
Concept ID:
C0037231
Disease or Syndrome
Sjogren-Larsson syndrome is an autosomal recessive, early childhood-onset disorder characterized by ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy. It is caused by deficiency of fatty aldehyde dehydrogenase (summary by Lossos et al., 2006).
Sturge-Weber syndrome
MedGen UID:
21361
Concept ID:
C0038505
Congenital Abnormality
Sturge-Weber syndrome is characterized by an intracranial vascular anomaly, leptomeningeal angiomatosis, most often involving the occipital and posterior parietal lobes. The most common symptoms and signs are facial cutaneous vascular malformations (port-wine stains), seizures, and glaucoma. Stasis results in ischemia underlying the leptomeningeal angiomatosis, leading to calcification and laminar cortical necrosis. The clinical course is highly variable and some children experience intractable seizures, mental retardation, and recurrent stroke-like episodes (review by Thomas-Sohl et al., 2004).
Lysosomal acid lipase deficiency
MedGen UID:
53088
Concept ID:
C0043208
Disease or Syndrome
Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease and cholesteryl ester storage disease (CESD). Wolman disease is an early-onset fulminant disorder of infancy with massive infiltration of the liver, spleen, and other organs by macrophages filled with cholesteryl esters and triglycerides. Death occurs early in life. Wolman disease is very rare, with an incidence of less than one in 100,000 live births. CESD is a milder, later-onset disorder with primary hepatic involvement by macrophages engorged with cholesteryl esters. This slowly progressive visceral disease has a very wide spectrum of involvement ranging from early onset with severe cirrhosis to later onset of more slowly progressive hepatic disease with survival into adulthood (summary by Du et al., 2001).
X-linked ichthyosis with steryl-sulfatase deficiency
MedGen UID:
86937
Concept ID:
C0079588
Disease or Syndrome
Ichthyosis is a genetically heterogeneous disorder of the skin. See, e.g., autosomal dominant ichthyosis vulgaris (146700), which is caused by mutations in the filaggrin gene (FLG; 135940). Ichthyosis can also be observed in multiple sulfatase deficiency (272200) (Shapiro, 1977). X-linked ichthyosis is fundamentally the same disorder as placental steroid sulfatase deficiency, which is often first noted in the pregnant mother of affected males by decreased estrogen or delayed progression of parturition (Alperin and Shapiro, 1997). This is thus an example of affinity ('lumping') of phenotypes thought previously to be separate, the opposite of genetic heterogeneity. Schnyder (1970) gave a useful classification of the inherited ichthyoses. Hernandez-Martin et al. (1999) provided a comprehensive review of X-linked ichthyosis. They pointed out that among all genetic disorders X-linked ichthyosis shows one of the highest ratios of chromosomal deletions; complete deletion has been found in up to 90% of patients.
Partial albinism
MedGen UID:
36361
Concept ID:
C0080024
Disease or Syndrome
Piebaldism is a rare autosomal dominant trait characterized by the congenital absence of melanocytes in affected areas of the skin and hair. A white forelock of hair, often triangular in shape, may be the only manifestation, or both the hair and the underlying forehead may be involved. The eyebrows and eyelashes may be affected. Irregularly shaped white patches may be observed on the face, trunk, and extremities, usually in a symmetrical distribution. Typically, islands of hyperpigmentation are present within and at the border of depigmented areas (summary by Thomas et al., 2004).
Mucopolysaccharidosis type VII
MedGen UID:
43108
Concept ID:
C0085132
Disease or Syndrome
Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993). MPS VII was the first autosomal mucopolysaccharidosis for which chromosomal assignment was achieved.
Proteus syndrome
MedGen UID:
39008
Concept ID:
C0085261
Neoplastic Process
Proteus syndrome is characterized by progressive, segmental or patchy overgrowth of diverse tissues of all germ layers, most commonly affecting the skeleton, skin, and adipose and central nervous systems. In most individuals Proteus syndrome has minimal or no manifestations at birth, develops and progresses rapidly beginning in the toddler period, and relentlessly progresses through childhood, causing severe overgrowth and disfigurement. It is associated with a range of tumors, pulmonary complications, and a striking predisposition to deep vein thrombosis and pulmonary embolism.
Hurler syndrome
MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes, Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome, no biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having either severe or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth ceases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life. Attenuated MPS I. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.
Hidrotic ectodermal dysplasia syndrome
MedGen UID:
56416
Concept ID:
C0162361
Congenital Abnormality
Hidrotic ectodermal dysplasia 2, or Clouston syndrome (referred to as HED2 throughout this GeneReview) is characterized by partial or total alopecia, dystrophy of the nails, hyperpigmentation of the skin (especially over the joints), and clubbing of the fingers. Sparse scalp hair and dysplastic nails are seen early in life. In infancy, scalp hair is wiry, brittle, patchy, and pale; progressive hair loss may lead to total alopecia by puberty. The nails may be milky white in early childhood; they gradually become dystrophic, thick, and distally separated from the nail bed. Palmoplantar keratoderma may develop during childhood and increases in severity with age. The clinical manifestations are highly variable even within the same family.
Angelman syndrome
MedGen UID:
58144
Concept ID:
C0162635
Disease or Syndrome
Angelman syndrome (AS) is characterized by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and/or tremulousness of the limbs, and a unique behavior with an inappropriate happy demeanor that includes frequent laughing, smiling, and excitability. Microcephaly and seizures are also common. Developmental delays are first noted at around age six months; however, the unique clinical features of AS do not become manifest until after age one year, and it can take several years before the correct clinical diagnosis is obvious.
Myoclonus with epilepsy with ragged red fibers
MedGen UID:
56486
Concept ID:
C0162672
Disease or Syndrome
A very rare mitochondrial abnormality characterized by myoclonic epilepsy and the microscopic finding of ragged-red fibers in muscle tissues.
Dubowitz's syndrome
MedGen UID:
59797
Concept ID:
C0175691
Congenital Abnormality
A syndrome of intrauterine dwarfism, short stature, mental retardation, sparse hair, eczema, and characteristic facies. The phenotype varies from normal growth and head circumference with mild psychomotor retardation and lack of eczema to severe growth and mental retardation, microcephaly, behavioral problems, aplastic anemia, immunological disorders, neoplasms, and eczema Some features of this syndrome are similar to those in Bloom and fetal alcohol syndromes.
Johanson-Blizzard syndrome
MedGen UID:
59798
Concept ID:
C0175692
Congenital Abnormality
Johanson-Blizzard syndrome is an autosomal recessive disorder characterized by poor growth, mental retardation, and variable dysmorphic features, including aplasia or hypoplasia of the nasal alae, abnormal hair patterns or scalp defects, and oligodontia. Other features include hypothyroidism, sensorineural hearing loss, imperforate anus, and pancreatic exocrine insufficiency (summary by Al-Dosari et al., 2008).
Saethre-Chotzen syndrome
MedGen UID:
64221
Concept ID:
C0175699
Congenital Abnormality
Classic Saethre-Chotzen syndrome (SCS) is characterized by coronal synostosis (unilateral or bilateral), facial asymmetry (particularly in individuals with unilateral coronal synostosis), ptosis, and characteristic appearance of the ear (small pinna with a prominent crus). Syndactyly of digits two and three of the hand is variably present. Intelligence is usually normal, although those with large genomic deletions are more likely to have developmental delays. Less common manifestations of SCS include short stature, parietal foramina, vertebral fusions, radioulnar synostosis, cleft palate, maxillary hypoplasia, ocular hypertelorism, hallux valgus, duplicated distal hallucal phalanx, and congenital heart malformations.
Williams syndrome
MedGen UID:
59799
Concept ID:
C0175702
Disease or Syndrome
Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvar aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty). Feeding difficulties often lead to failure to thrive in infancy. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones.
Aicardi's syndrome
MedGen UID:
61236
Concept ID:
C0175713
Disease or Syndrome
Aicardi syndrome was classically characterized by a triad of features: agenesis of the corpus callosum, distinctive chorioretinal lacunae, and infantile spasms. However, it is now well recognized that several other important findings are typically present in girls with Aicardi syndrome. Neurologic examination can reveal microcephaly, axial hypotonia, and appendicular hypertonia with spasticity. Moderate to severe global developmental delay and intellectual disability are expected. Many girls with Aicardi syndrome develop seizures prior to age three months, and most before age one year. Ongoing medically refractory epilepsy with a variety of seizure types develops over time. Costovertebral defects are common and can lead to marked scoliosis in up to one third of affected individuals. Other features include characteristic facial features, gastrointestinal difficulties, small hands, vascular malformations and pigmentary lesions of the skin, increased incidence of tumors, lower growth rate after ages seven to nine years, and precocious or delayed puberty. Survival is highly variable, with the mean age of death about 8.3 years and the median age of death about 18.5 years.
Progressive sclerosing poliodystrophy
MedGen UID:
60012
Concept ID:
C0205710
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. These phenotypes exemplify the diversity that can result from mutation of a given gene. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life up to about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, Parkinsonism, hypogonadism, and cataracts (in what has been called “chronic progressive external ophthalmoplegia plus,” or “CPEO+”).
Choroid plexus papilloma
MedGen UID:
64439
Concept ID:
C0205770
Neoplastic Process
Choroid plexus tumors are of neuroectodermal origin and range from benign choroid plexus papillomas (CPPs) to malignant choroid carcinomas (CPCs). These rare tumors generally occur in childhood, but have also been reported in adults. Patients typically present with signs and symptoms of increased intracranial pressure including headache, hydrocephalus, papilledema, nausea, vomiting, cranial nerve deficits, gait impairment, and seizures (summary by Safaee et al., 2013).
Spongy degeneration of central nervous system
MedGen UID:
61565
Concept ID:
C0206307
Disease or Syndrome
Neonatal/infantile (severe) Canavan disease is characterized by macrocephaly, lack of head control, and developmental delays usually noted by age three to five months. As children get older hypotonia becomes severe and failure to achieve independent sitting, ambulation, or speech become apparent. Hypotonia eventually changes to spasticity. Assistance with feeding becomes necessary. Life expectancy is usually into the teens. Mild/juvenile Canavan disease is characterized by mild developmental delay that can go unrecognized. Head circumference may be normal.
Microsomia hemifacial radial defects
MedGen UID:
67392
Concept ID:
C0220681
Disease or Syndrome
KBG syndrome
MedGen UID:
66317
Concept ID:
C0220687
Disease or Syndrome
KBG syndrome is characterized by macrodontia of the upper central incisors, distinctive craniofacial findings, short stature, skeletal anomalies, and neurologic involvement that includes global developmental delay, seizures, and intellectual disability (summary by Sirmaci et al., 2011). Sirmaci et al. (2011) noted that it is likely that KBG syndrome is underdiagnosed, since many of the features, including intellectual disability, are mild, and none of the features is a prerequisite for diagnosis.
Fryns syndrome
MedGen UID:
65088
Concept ID:
C0220730
Disease or Syndrome
Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia or agenesis); characteristic facial appearance (coarse facies, ocular hypertelorism, broad and flat nasal bridge, thick nasal tip, long philtrum, low-set and poorly formed ears, tented upper lip, macrostomia, micrognathia); distal digital hypoplasia (nails, terminal phalanges); pulmonary hypoplasia; and associated anomalies (polyhydramnios, cloudy corneas and/or microphthalmia, orofacial clefting, renal dysplasia/renal cortical cysts, and/or malformations involving the brain, cardiovascular system, gastrointestinal system, genitalia). Survival beyond the neonatal period has been rare. Data on postnatal growth and psychomotor development are limited; however, severe developmental delay and intellectual disability are common.
Bixler Christian Gorlin syndrome
MedGen UID:
113104
Concept ID:
C0220742
Disease or Syndrome
Metaphyseal chondrodysplasia, McKusick type
MedGen UID:
67398
Concept ID:
C0220748
Congenital Abnormality
The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes: Metaphyseal dysplasia without hypotrichosis (MDWH), Cartilage-hair hypoplasia (CHH), and Anauxetic dysplasia (AD). CHH-AD spectrum disorders are characterized by severe disproportionate (short-limb) short stature which is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility and often fine silky hair, immunodeficiency, anemia, impaired spermatogenesis, gastrointestinal dysfunction, and increased risk for malignancy. The most severe phenotype (AD), which has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn and may include cognitive deficiency. The clinical manifestations of the CHH-AD spectrum disorders are variable, even within the same family.
Craniofrontonasal dysplasia
MedGen UID:
65095
Concept ID:
C0220767
Disease or Syndrome
Craniofrontonasal syndrome is an X-linked developmental disorder that shows paradoxically greater severity in heterozygous females than in hemizygous males. Females have frontonasal dysplasia, craniofacial asymmetry, craniosynostosis, bifid nasal tip, grooved nails, wiry hair, and abnormalities of the thoracic skeleton, whereas males typically show only hypertelorism (Twigg et al., 2004; Wieland et al., 2004).
Acquired partial lipodystrophy
MedGen UID:
66352
Concept ID:
C0220989
Disease or Syndrome
Acquired partial lipodystrophy is characterized clinically by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the 'cephalocaudal' sequence, sparing the lower extremities (summary by Misra et al., 2004). The disorder is not inherited in a classic mendelian pattern; it rather represents a phenotype with a complex etiology. Affected individuals may have genetic susceptibility factors that require the additional presence of environmental factors or acquired disorders to be expressed (summary by Hegele et al., 2006). Most cases are sporadic, family history is negative, and females are more often affected than males (ratio, 4:1). There is an association between APLD and autoimmune diseases (Misra and Garg, 2003; Misra et al., 2004), and a subset of patients have APLD associated with low serum complement component C3 and the autoantibody C3 nephritic factor, with or without membranoproliferative glomerulonephritis (APLDC3; 613913). Acquired partial lipodystrophy is distinct from inherited forms of partial lipodystrophy, which are metabolic disorders that show clear mendelian inheritance (see, e.g., FPLD1, 608600).
Abortive cerebellar ataxia
MedGen UID:
66358
Concept ID:
C0221061
Disease or Syndrome
'Behr syndrome' is a clinical term that refers to the constellation of early-onset optic atrophy accompanied by neurologic features, including ataxia, pyramidal signs, spasticity, and mental retardation (Behr, 1909; Thomas et al., 1984). Type III 3-methylglutaconic aciduria (258501) shows a very similar clinical phenotype, with the addition of increased urinary 3-methylglutaconic acid. It is most common in individuals of Iraqi Jewish origin. However, Lerman-Sagie (1995) noted that this abnormal urinary pattern may not be picked up by routine organic acid analysis, suggesting that early reports of Behr syndrome with normal metabolic features may have actually been 3-methylglutaconic aciduria type III.
Cholestanol storage disease
MedGen UID:
116041
Concept ID:
C0238052
Disease or Syndrome
Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease characterized by infantile-onset diarrhea, childhood-onset cataract, adolescent- to young adult-onset tendon xanthomas, and adult-onset progressive neurologic dysfunction (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, dystonia, atypical parkinsonism, peripheral neuropathy, and seizures). Chronic diarrhea from infancy may be the earliest clinical manifestation. In approximately 75% of affected individuals, cataracts are the first finding, often appearing in the first decade of life. Xanthomas appear in the second or third decade; they occur on the Achilles tendon, the extensor tendons of the elbow and hand, the patellar tendon, and the neck tendons. Xanthomas have been reported in the lung, bones, and central nervous system. Some individuals show mental impairment from early infancy, whereas the majority have normal or only slightly subnormal intellectual function until puberty; dementia with slow deterioration in intellectual abilities occurs in the 20s in more than 50% of individuals. Neuropsychiatric symptoms such as behavioral changes, hallucinations, agitation, aggression, depression, and suicide attempts may be prominent. Pyramidal signs (i.e., spasticity) and/or cerebellar signs almost invariably become evident between ages 20 and 30 years.
Ganglioside sialidase deficiency
MedGen UID:
68663
Concept ID:
C0238286
Disease or Syndrome
Mucolipidosis IV is characterized by severe psychomotor delay evident by the end of the first year of life and slowly progressive visual impairment during the first decade as a result of a combination of corneal clouding and retinal degeneration. By the end of the first decade of life and certainly by their early teens, all individuals with typical mucolipidosis IV have severe visual impairment as a result of retinal degeneration. Neurodegeneration is thought to occur in no more than 15% of individuals. About 5% of individuals have atypical mucolipidosis IV, often manifest as less severe psychomotor retardation and/or eye findings. About 70% of individuals with mucolipidosis IV are of Ashkenazi Jewish heritage.
Pyknodysostosis
MedGen UID:
116061
Concept ID:
C0238402
Congenital Abnormality
Rare autosomal recessive syndrome characterized by delayed closing of CRANIAL SUTURES, short stature, ACRO-OSTEOLYSIS of distal phalanges, dental and MAXILLOFACIAL ABNORMALITIES and an increase in bone density that results in frequent BONE FRACTURES. It is associated with BONE RESORPTION defect due to mutations in the lysosomal cysteine protease CATHEPSIN K.
Weaver syndrome
MedGen UID:
120511
Concept ID:
C0265210
Congenital Abnormality
EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with heterozygous EZH2 pathogenic variants is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Neuronal migration disorders have also been reported in a few individuals with EZH2-related overgrowth. Malignancies (including neuroblastoma and hematologic malignancies) may occur with increased frequently; current data are insufficient to draw conclusions.
Marshall-Smith syndrome
MedGen UID:
75551
Concept ID:
C0265211
Congenital Abnormality
The Marshall-Smith syndrome is a malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia (Adam et al., 2005).
X-linked hydrocephalus syndrome
MedGen UID:
75552
Concept ID:
C0265216
Disease or Syndrome
The phenotypic spectrum of L1 syndrome includes: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS); MASA syndrome (mental retardation, aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs); SPG1 (X-linked complicated hereditary spastic paraplegia type 1); and X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50).
Pallister-Hall syndrome
MedGen UID:
120514
Concept ID:
C0265220
Disease or Syndrome
Pallister-Hall syndrome (referred to as PHS in this entry) is characterized by a spectrum of anomalies ranging from polydactyly, asymptomatic bifid epiglottis, and hypothalamic hamartoma at the mild end to laryngotracheal cleft with neonatal lethality at the severe end. Individuals with mild PHS may be incorrectly diagnosed as having isolated postaxial polydactyly type A. Individuals with PHS can have pituitary insufficiency and may die as neonates from undiagnosed and untreated adrenal insufficiency.
Cohen syndrome
MedGen UID:
78539
Concept ID:
C0265223
Disease or Syndrome
Cohen syndrome is characterized by failure to thrive in infancy and childhood; truncal obesity in the teen years; early-onset hypotonia and developmental delays; microcephaly developing during the first year of life; moderate to profound psychomotor retardation; progressive retinochoroidal dystrophy and high myopia; neutropenia in many with recurrent infections and aphthous ulcers in some; a cheerful disposition; joint hypermobility; and characteristic facial features.
Cryptophthalmos syndrome
MedGen UID:
82692
Concept ID:
C0265233
Congenital Abnormality
Fraser syndrome is a rare disorder that affects development starting before birth. Characteristic features of this condition include eyes that are completely covered by skin and usually malformed (cryptophthalmos), fusion of the skin between the fingers and toes (cutaneous syndactyly), and abnormalities of the genitalia and the urinary tract (genitourinary anomalies). Other tissues and organs can also be affected. Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth; less severely affected individuals can live into childhood or adulthood. Cryptophthalmos is the most common abnormality in people with Fraser syndrome. Both eyes are usually completely covered by skin, but in some cases, only one eye is covered or one or both eyes are partially covered. In cryptophthalmos, the eyes can also be malformed; for example, the eyeballs may be fused to the skin covering them, or they may be small (microphthalmia) or missing (anophthalmia). Eye abnormalities typically lead to impairment or loss of vision in people with Fraser syndrome. Affected individuals can have other problems related to abnormal eye development, including missing eyebrows or eyelashes or a patch of hair extending from the side hairline to the eyebrow. Cutaneous syndactyly typically occurs in both the hands and the feet in Fraser syndrome. In most people with this feature, the skin between the middle three fingers and toes are fused, but the other digits can also be involved. Other abnormalities of the hands and feet can occur in people with Fraser syndrome. Individuals with Fraser syndrome can have abnormalities of the genitalia, such as an enlarged clitoris in females or undescended testes (cryptorchidism) in males. Some affected individuals have external genitalia that do not appear clearly female or male (ambiguous genitalia). The most common urinary tract abnormality in Fraser syndrome is the absence of one or both kidneys (renal agenesis). Affected individuals can have other kidney problems or abnormalities of the bladder and other parts of the urinary tract. A variety of other signs and symptoms can be involved in Fraser syndrome, including heart malformations or abnormalities of the voicebox (larynx) or other parts of the respiratory tract. Some affected individuals have facial abnormalities, including ear or nose abnormalities or an opening in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).
Goldenhar syndrome
MedGen UID:
75554
Concept ID:
C0265240
Congenital Abnormality
Craniofacial microsomia (CFM) includes a spectrum of malformations primarily involving structures derived from the first and second branchial arches. Characteristic findings include facial asymmetry resulting from maxillary and/or mandibular hypoplasia; preauricular or facial tags; ear malformations that can include microtia (hypoplasia of the external ear), anotia (absence of the external ear), or aural atresia (absence of the external ear canal); and hearing loss. Severity can range from subtle facial asymmetry with a small skin tag in front of an otherwise normal-appearing ear to bilateral involvement (typically asymmetric), microtia/anotia with atresia of the ear canals, microphthalmia, and respiratory compromise from severe mandibular hypoplasia. Other craniofacial malformations including cleft lip and/or palate can be seen. Non-craniofacial malformations, especially vertebral, renal, cardiac, and limb, can be seen.
Townes syndrome
MedGen UID:
75555
Concept ID:
C0265246
Disease or Syndrome
Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (82%), dysplastic ears (88%) (overfolded superior helices and preauricular tags) frequently associated with sensorineural and/or conductive hearing impairment (65%), and thumb malformations (89%) (triphalangeal thumbs, duplication of the thumb (preaxial polydactyly), and rarely hypoplasia of the thumbs). Renal impairment (27%), including end-stage renal disease (ESRD) (42%), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%. Foot malformations (52%) (flat feet, overlapping toes) and genitourinary malformations (36%) are common. Intellectual disability occurs in approximately 10% of cases. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation.
Ruvalcaba syndrome
MedGen UID:
120520
Concept ID:
C0265248
Disease or Syndrome
A dysmorphic syndrome characterized by short stature, microcephaly, mental deficiency, peculiar facies, hypoplastic genitalia, and skeletal anomalies.
Mietens syndrome
MedGen UID:
82695
Concept ID:
C0265249
Disease or Syndrome
Mild mental deficiency with growth retardation, ocular defects, and limb abnormalities.
Coffin-Lowry syndrome
MedGen UID:
75556
Concept ID:
C0265252
Disease or Syndrome
Coffin-Lowry syndrome (CLS) is usually characterized by severe-to-profound intellectual disability in males; less severely impaired individuals have been reported. Intellect ranges from normal to profoundly impaired in heterozygous females. The facial appearance is characteristic in the affected, older male child or adult. The hands are short, soft, and fleshy, often with remarkably hyperextensible fingers that taper from wide (proximally) to narrow with small terminal phalanges and nails. Males are consistently below the third centile in height. Microcephaly is common. Cardiac abnormalities may be present and can contribute to premature death. Stimulus-induced drop attacks (SIDAs) in which unexpected tactile or auditory stimuli or excitement triggers a brief collapse but no loss of consciousness are present in approximately 20% of affected individuals. Typically SIDAs begin between mid-childhood and the teens. Progressive kyphoscoliosis is one of the most difficult aspects of long-term care. Life span may be reduced.
Popliteal pterygium syndrome
MedGen UID:
78543
Concept ID:
C0265259
Congenital Abnormality
IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end. Individuals with VWS show one or more of the following anomalies: Congenital, usually bilateral, paramedian lower-lip fistulae (pits) or sometimes small mounds with a sinus tract leading from a mucous gland of the lip. Cleft lip (CL). Cleft palate (CP)?Note: Cleft lip with or without cleft palate (CL±P) is observed about twice as often as CP only. Submucous cleft palate (SMCP). The PPS phenotype includes the following: CL±P . Fistulae of the lower lip . Webbing of the skin extending from the ischial tuberosities to the heels . In males: bifid scrotum and cryptorchidism. In females: hypoplasia of the labia majora. Syndactyly of fingers and/or toes . Anomalies of the skin around the nails. A characteristic pyramidal fold of skin overlying the nail of the hallux (almost pathognomonic) . In some non-classic forms of PPS: filiform synechiae connecting the upper and lower jaws (syngnathia) or the upper and lower eyelids (ankyloblepharon) . In both VWS and PPS, growth and intelligence are normal.
Multiple pterygium syndrome Escobar type
MedGen UID:
82696
Concept ID:
C0265261
Congenital Abnormality
Multiple pterygium syndromes comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis) (Morgan et al., 2006). The multiple pterygium syndromes are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal (253290) and nonlethal (Escobar) types.
Child syndrome
MedGen UID:
82697
Concept ID:
C0265267
Disease or Syndrome
The NSDHL-related disorders include: CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, an X-linked dominant condition that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked recessive disorder that affects males. CHILD syndrome is characterized by unilateral distribution of ichthyosiform (yellow scaly) skin lesions and ipsilateral limb defects that range from shortening of the metacarpals and phalanges to absence of the entire limb. Intellect is usually normal. The ichthyosiform skin lesions are usually present at birth or in the first weeks of life; new lesions can develop in later life. Nail changes are also common. The heart, lung, and kidneys can also be involved. CK syndrome (named for the initials of the original proband) is characterized by mild to severe cognitive impairment and behavior problems (aggression, attention deficit hyperactivity disorder [ADHD], and irritability). All affected males reported have developed seizures in infancy and have cerebral cortical malformations and microcephaly. All have distinctive facial features, a thin habitus, and relatively long, thin fingers and toes. Some have scoliosis and kyphosis.
Sclerosteosis
MedGen UID:
120530
Concept ID:
C0265301
Congenital Abnormality
SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease; both are disorders of osteoblast hyperactivity. The major clinical features of sclerosteosis are progressive skeletal overgrowth and variable syndactyly, usually of the second (index) and third (middle) fingers. Affected individuals appear normal at birth except for syndactyly. Distinctive facial features including asymmetric mandibular hypertrophy, frontal bossing, and midface hypoplasia are usually apparent by mid-childhood. Hyperostosis of the skull results in narrowing of the foramina, causing entrapment of the seventh cranial nerve (often leading to facial palsy) and entrapment of the eighth cranial nerve (often resulting in deafness in mid-childhood). In sclerosteosis, hyperostosis of the calvarium reduces intracranial volume, increasing the risk for potentially lethal elevation of intracranial pressure. Survival of individuals with sclerosteosis into old age is unusual. The manifestations of van Buchem disease are generally milder than sclerosteosis and syndactyly is absent. Based on a few case reports, it is also likely that the spectrum of SOST-related sclerosing bone dysplasias includes an autosomal dominant form of craniodiaphyseal dysplasia (CDD).
Greig cephalopolysyndactyly syndrome
MedGen UID:
120531
Concept ID:
C0265306
Disease or Syndrome
Typical Greig cephalopolysyndactyly syndrome (GCPS) is characterized by preaxial polydactyly or mixed pre- and postaxial polydactyly, true widely spaced eyes, and macrocephaly. Individuals with mild GCPS may have subtle craniofacial findings. The mild end of the GCPS spectrum is a continuum with preaxial polysyndactyly type IV and crossed polydactyly (preaxial polydactyly of the feet and postaxial polydactyly of the hands plus syndactyly of fingers 3-4 and toes 1-3). Individuals with severe GCPS can have seizures, hydrocephalus, and intellectual disability.
Epidermal nevus syndrome
MedGen UID:
120533
Concept ID:
C0265318
Disease or Syndrome
Schimmelpenning-Feuerstein-Mims syndrome, also known as linear sebaceous nevus syndrome, is characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects (summary by Happle, 1991 and Ernst et al., 2007). The linear sebaceous nevi follow the lines of Blaschko (Hornstein and Knickenberg, 1974; Bouwes Bavinck and van de Kamp, 1985). All cases are sporadic. The syndrome is believed to be caused by an autosomal dominant lethal mutation that survives by somatic mosaicism (Gorlin et al., 2001).
Bannayan-Riley-Ruvalcaba syndrome
MedGen UID:
78554
Concept ID:
C0265326
Congenital Abnormality
The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and Proteus-like syndrome. CS is a multiple hamartoma syndrome with a high risk for benign and malignant tumors of the thyroid, breast, and endometrium. Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules, and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age of diagnosis between 38 and 46 years. The lifetime risk for thyroid cancer (usually follicular, rarely papillary, but never medullary thyroid cancer) is approximately 35%. The risk for endometrial cancer, although not well defined, may approach 28%. BRRS is a congenital disorder characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis. PS is a complex, highly variable disorder involving congenital malformations and hamartomatous overgrowth of multiple tissues, as well as connective tissue nevi, epidermal nevi, and hyperostoses. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of PS who do not meet the diagnostic criteria for PS.
Moynahan's syndrome
MedGen UID:
120535
Concept ID:
C0265328
Congenital Abnormality
Alopecia or hypotrichosis, microcephaly, seizures, and mental retardation. A suggested classification groups this syndrome into three types: Type I. Total alopecia and mental retardation, the main features, in association with microcephaly. Type II. Subtotal alopecia and mental retardation with or without epilepsy. Type III. Subtotal alopecia and psychomotor retardation with microcephaly and epilepsy.
Borjeson-Forssman-Lehmann syndrome
MedGen UID:
78557
Concept ID:
C0265339
Disease or Syndrome
Microcephaly, characteristic facies (swelling, p prominent supraorbital ridges and narrow palpebral fissures), obesity, epilepsy, and hypogonadism, and mental deficiency.
Cerebro-costo-mandibular syndrome
MedGen UID:
120537
Concept ID:
C0265342
Disease or Syndrome
Cerebrocostomandibular syndrome (CCMS) is characterized mainly by severe micrognathia, rib defects, and mental retardation. A spectrum of rib gap defects have been reported ranging from a few dorsal rib segments to complete absence of ossification. In about half of the 65 reported cases to date, there is cerebral involvement including mental retardation, microcephaly, and histologic anomalies. Both autosomal dominant and recessive inheritance has been described (Zeevaert et al., 2009). See CDG2G (611209) for a cerebrocostomandibular-like syndrome.
Leprechaunism syndrome
MedGen UID:
82708
Concept ID:
C0265344
Disease or Syndrome
Donohue syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. Severe insulin resistance leads to problems with regulating blood sugar levels and affects the development and function of organs and tissues throughout the body. Severe insulin resistance underlies the varied signs and symptoms of Donohue syndrome. Individuals with Donohue syndrome are unusually small starting before birth, and affected infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features that become apparent soon after birth include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Donohue syndrome include bulging eyes, thick lips, upturned nostrils, and low-set ears. Affected individuals develop recurrent, life-threatening infections beginning in infancy. Donohue syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Rabson-Mendenhall syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Donohue syndrome represents the most severe end of the spectrum; children with this condition do not survive beyond age 2.
CHARGE association
MedGen UID:
75567
Concept ID:
C0265354
Congenital Abnormality
CHARGE is a mnemonic for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies. CHARGE syndrome is characterized by the following: Unilateral or bilateral coloboma of the iris, retina-choroid, and/or disc with or without microphthalmos (80%-90% of individuals). Unilateral or bilateral choanal atresia or stenosis (50%-60%). Cranial nerve dysfunction resulting in hyposmia or anosmia, unilateral or bilateral facial palsy (40%), impaired hearing, and/or swallowing problems (70%-90%). Abnormal outer ears, ossicular malformations, Mondini defect of the cochlea and absent or hypoplastic semicircular canals (>90%). Cryptorchidism in males and hypogonadotrophic hypogonadism in both males and females. Developmental delay. Cardiovascular malformations (75%-85%). Growth deficiency (70%-80%). Orofacial clefts (15%-20%). Tracheoesophageal fistula (15%-20%) . Neonates with CHARGE syndrome often have multiple life-threatening medical conditions. Feeding difficulties are a major cause of morbidity in all age groups.
Fetal trimethadione syndrome
MedGen UID:
120538
Concept ID:
C0265373
Congenital Abnormality
A pattern of abnormalities in infants born to epileptic mothers who were treated during their pregnancies with trimethadione anticonvulsant drugs. The abnormalities include developmental delay, craniofacial dysmorphism (midfacial flattening, V-shaped eyebrows, short nose, synophrys, malformed ears, and strabismus), cardiovascular abnormalities, absent kidney and ureter, omphalocele, meningocele, and other defects.
Pallister-Killian syndrome
MedGen UID:
120540
Concept ID:
C0265449
Disease or Syndrome
Pallister-Killian syndrome is a dysmorphic condition involving most organ systems, but also characterized by a tissue-limited mosaicism; most fibroblasts have 47 chromosomes with an extra small metacentric chromosome, whereas the karyotype of lymphocytes is normal. The extra metacentric chromosome is an isochromosome for part of the short arm of chromosome 12: i(12)(p10) (Peltomaki et al., 1987; Warburton et al., 1987).
13q partial monosomy syndrome
MedGen UID:
120541
Concept ID:
C0265451
Disease or Syndrome
The chromosome 13q14 deletion syndrome is characterized by retinoblastoma (180200), variable degrees of mental impairment, and characteristic facial features, including high forehead, prominent philtrum, and anteverted earlobes (summary by Caselli et al., 2007).
Cat eye syndrome
MedGen UID:
120543
Concept ID:
C0265493
Disease or Syndrome
Cat eye syndrome (CES) is characterized clinically by the combination of coloboma of the iris and anal atresia with fistula, downslanting palpebral fissures, preauricular tags and/or pits, frequent occurrence of heart and renal malformations, and normal or near-normal mental development. A small supernumerary chromosome (smaller than chromosome 21) is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11).
Scaphycephaly
MedGen UID:
82712
Concept ID:
C0265534
Congenital Abnormality
Premature fusion of the sagittal suture.
Erythrokeratodermia variabilis
MedGen UID:
75587
Concept ID:
C0265961
Congenital Abnormality
The erythrokeratodermias are a clinically variable and genetically heterogeneous group of inherited disorders characterized by widespread erythematous plaques, stationary or migratory, associated with nonmigratory hyperkeratoses (summary by Ishida-Yamamoto et al., 1997). The condition is usually present at birth or occurs during the first year but may begin later in childhood or even in early adulthood. Lesions preferentially affect the face, buttocks, and extensor surfaces of the limbs. Palmoplantar keratoderma occurs in about half the cases, but hair, nails, and teeth are not affected (summary by Macfarlane et al., 1991).
Netherton syndrome
MedGen UID:
78578
Concept ID:
C0265962
Disease or Syndrome
Netherton syndrome is a disorder that affects the skin, hair, and immune system. Newborns with Netherton syndrome have skin that is red and scaly (ichthyosiform erythroderma), and the skin may leak fluid. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis), which can be life-threatening. Affected babies may also fail to grow and gain weight at the expected rate (failure to thrive). The health of older children and adults with Netherton syndrome usually improves, although they often remain underweight and of short stature. After infancy, the severity of the skin abnormalities varies among people with Netherton syndrome and can fluctuate over time. The skin may continue to be red and scaly, especially during the first few years of life. Some affected individuals have intermittent redness or experience outbreaks of a distinctive skin abnormality called ichthyosis linearis circumflexa, involving patches of multiple ring-like lesions. The triggers for the outbreaks are not known, but researchers suggest that stress or infections may be involved. Itchiness is a common problem for affected individuals, and scratching can lead to frequent infections. Dead skin cells are shed at an abnormal rate and often accumulate in the ear canals, which can affect hearing if not removed regularly. The skin is abnormally absorbent of substances such as lotions and ointments, which can result in excessive blood levels of some topical medications. Because the ability of the skin to protect against heat and cold is impaired, affected individuals may have difficulty regulating their body temperature. People with Netherton syndrome have hair that is fragile and breaks easily. Some strands of hair vary in diameter, with thicker and thinner spots. This feature is known as bamboo hair, trichorrhexis nodosa, or trichorrhexis invaginata. In addition to the hair on the scalp, the eyelashes and eyebrows may be affected. The hair abnormality in Netherton syndrome may not be noticed in infancy because babies often have sparse hair. Most people with Netherton syndrome have immune system-related problems such as food allergies, hay fever, asthma, or an inflammatory skin disorder called eczema.
Mutilating keratoderma
MedGen UID:
78579
Concept ID:
C0265964
Congenital Abnormality
Vohwinkel syndrome is a disorder with classic and variant forms, both of which affect the skin. In the classic form of Vohwinkel syndrome, affected individuals have thick, honeycomb-like calluses on the palms of the hands and soles of the feet (palmoplantar keratoses) beginning in infancy or early childhood. Affected children also typically have distinctive starfish-shaped patches of thickened skin on the tops of the fingers and toes or on the knees. Within a few years they develop tight bands of abnormal fibrous tissue around their fingers and toes (pseudoainhum); the bands may cut off the circulation to the digits and result in spontaneous amputation. People with the classic form of the disorder also have hearing loss. The variant form of Vohwinkel syndrome does not involve hearing loss, and the skin features also include widespread dry, scaly skin (ichthyosis), especially on the limbs. The ichthyosis is usually mild, and there may also be mild reddening of the skin (erythroderma). Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life.
Congenital cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Hypoplasia of the cerebellum that is associated with inherited metabolic disorders and neurodegenerative disorders. Signs and symptoms include mental and developmental delays, walking and balance difficulties, floppy muscle tone, and seizures.
Schizencephaly
MedGen UID:
78606
Concept ID:
C0266484
Disease or Syndrome
Brunelli et al. (1996) described schizencephaly as an extremely rare congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. The clefts are lined with gray matter and most commonly involve the parasylvian regions (Wolpert and Barnes, 1992). Large portions of the cerebral hemispheres may be absent and replaced by cerebrospinal fluid. Two types of schizencephaly have been described, depending on the size of the area involved and the separation of the cleft lips (Wolpert and Barnes, 1992). Type I schizencephaly consists of a fused cleft. This fused pial-ependymal seam forms a furrow in the developing brain, and is lined by polymicrogyric gray matter. In type II schizencephaly, there is a large defect, a holohemispheric cleft in the cerebral cortex filled with fluid and lined by polymicrogyric gray matter. The clinical manifestations depend on the severity of the lesion. Patients with type I are often almost normal; they may have seizures and spasticity. In type II abnormalities, there is usually mental retardation, seizures, hypotonia, spasticity, inability to walk or speak, and blindness. Schizencephaly may be part of the larger phenotypic spectrum of holoprosencephaly (HPE; see 236100).
Atrophia bulborum hereditaria
MedGen UID:
75615
Concept ID:
C0266526
Congenital Abnormality
NDP-related retinopathies are characterized by a spectrum of fibrous and vascular changes of the retina at birth that progress through childhood or adolescence to cause varying degrees of visual impairment. The most severe phenotype is described as Norrie disease (ND), characterized by greyish yellow fibrovascular masses (pseudogliomas) secondary to retinal vascular dysgenesis and detachment. Congenital blindness is almost always present. Approximately 30%-50% of males with ND have developmental delay/intellectual disability, behavioral abnormalities, or psychotic-like features. The majority of males with ND develop sensorineural hearing loss. Less severe phenotypes include: persistent hyperplastic primary vitreous (PHPV), characterized by a fibrotic white stalk from the optic disk to the lens; X-linked familial exudative vitreoretinopathy (XL-FEVR), characterized by peripheral retinal vascular anomalies with or without fibrotic changes and retinal detachment; retinopathy of prematurity (ROP); and Coats disease, an exudative proliferative vasculopathy. Phenotypes can vary within families.
Orotic aciduria
MedGen UID:
78642
Concept ID:
C0268128
Disease or Syndrome
Orotic aciduria is a rare autosomal recessive disorder characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Bailey (2009) reported that to that time, 2 cases of orotic aciduria without megaloblastic anemia (OAWA) had been reported.
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
MedGen UID:
82777
Concept ID:
C0268151
Disease or Syndrome
The term galactosemia refers to disorders of galactose metabolism that include classic galactosemia, clinical variant galactosemia, and biochemical variant galactosemia. This GeneReview focuses on: Classic galactosemia, which can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage, bleeding, and E. coli sepsis in untreated infants. If a lactose-restricted diet is provided during the first ten days of life, the neonatal signs usually quickly resolve and the complications of liver failure, sepsis, and neonatal death are prevented; however, despite adequate treatment from an early age, children with classic galactosemia remain at increased risk for developmental delays, speech problems (termed childhood apraxia of speech and dysarthria), and abnormalities of motor function. Almost all females with classic galactosemia manifest premature ovarian insufficiency (POI). Clinical variant galactosemia, which can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage including cirrhosis and bleeding in untreated infants. This is exemplified by the disease that occurs in African Americans and native Africans in South Africa. Persons with clinical variant galactosemia may be missed with newborn screening (NBS) as the hypergalactosemia is not as marked as in classic galactosemia and breath testing is normal. If a lactose-restricted diet is provided during the first ten days of life, the severe acute neonatal complications are usually prevented. African Americans with clinical variant galactosemia and adequate early treatment do not appear to be at risk for long-term complications including POI.
Deficiency of cytochrome-b5 reductase
MedGen UID:
75661
Concept ID:
C0268193
Disease or Syndrome
Methemoglobinemia due to NADH-cytochrome b5 reductase deficiency is an autosomal recessive disorder characterized clinically by decreased oxygen carrying capacity of the blood, with resultant cyanosis and hypoxia (review by Percy and Lappin, 2008). There are 2 types of methemoglobin reductase deficiency. In type I, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type II, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes, and all body tissues. Type II methemoglobinemia is associated with mental deficiency and other neurologic symptoms. The neurologic symptoms may be related to the major role played by the cytochrome b5 system in the desaturation of fatty acids (Vives-Corrons et al., 1978; Kaplan et al., 1979).
Aspartylglycosaminuria
MedGen UID:
78649
Concept ID:
C0268225
Disease or Syndrome
Aspartylglucosaminuria is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive mental retardation. The disorder is caused by deficient activity of the lysosomal enzyme glycosylasparaginase, which results in body fluid and tissue accumulation of a series of glycoasparagines, i.e., glycoconjugates with an aspartylglucosamine moiety at the reducing end. AGU belongs to the group of disorders commonly referred to as the Finnish disease heritage (summary by Mononen et al., 1993 and Arvio and Arvio, 2002).
Sialidosis, type II
MedGen UID:
120621
Concept ID:
C0268226
Disease or Syndrome
Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (604369) is a form of 'free' sialic acid disease. Classification Lowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.
Combined deficiency of sialidase AND beta galactosidase
MedGen UID:
82779
Concept ID:
C0268233
Disease or Syndrome
Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase (611458) and neuraminidase (608272), secondary to a defect in protective protein/cathepsin A (PPCA). All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and rare occurrence of neurologic signs. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. The majority of reported patients belong to the juvenile/adult group and are mainly of Japanese origin (summary by d'Azzo et al., 2001).
Farber's lipogranulomatosis
MedGen UID:
78654
Concept ID:
C0268255
Disease or Syndrome
Farber lipogranulomatosis is an autosomal recessive lysosomal storage disorder characterized by early-onset subcutaneous nodules, painful and progressively deformed joints, and hoarseness by laryngeal involvement. Based on the age of onset, the severity of symptoms, and the difference in organs affected, 6 clinical subtypes due to deficiency of acid ceramidase have been distinguished. The most severe form is subtype 4, a rare neonatal form of the disease with death occurring before 1 year of age (summary by Alves et al., 2013).
Multiple sulfatase deficiency
MedGen UID:
75664
Concept ID:
C0268263
Disease or Syndrome
Multiple sulfatase deficiency is an autosomal recessive inborn error of metabolism resulting in tissue accumulation of sulfatides, sulfated glycosaminoglycans, sphingolipids, and steroid sulfates. The enzymatic defect affects the whole family of sulfatase enzymes; thus, the disorder combines features of metachromatic leukodystrophy (250100) and of various mucopolysaccharidoses (see, e.g., MPS6; 253200). Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and ichthyosis. Different types of MSD can be distinguished according to the age of onset: neonatal, late infantile (0 to 2 years), and juvenile (2 to 4 years). Neonatal MSD is the most severe form with a broad range of mucopolysaccharidosis-like symptoms and death within the first year of life. Late-infantile MSD, which includes the majority of cases, resembles late-infantile metachromatic leukodystrophy with progressive loss of mental and motor abilities and skeletal changes. There is also an attenuated form of late-infantile MSD with onset beyond the second year of life. Rare cases of juvenile-onset MSD have been reported with onset of symptoms in late childhood and slower progression (Blanco-Aguirre et al., 2001) (summary by Schlotawa et al., 2011).
Ehlers-Danlos syndrome, type 4
MedGen UID:
82790
Concept ID:
C0268338
Disease or Syndrome
Ehlers-Danlos syndrome type IV (EDS type IV) is characterized by thin, translucent skin; easy bruising; characteristic facial appearance (in some individuals); and arterial, intestinal, and/or uterine fragility. Vascular dissection or rupture, gastrointestinal perforation, or organ rupture are the presenting signs in the majority of adults identified to have EDS type IV. Arterial rupture may be preceded by aneurysm, arteriovenous fistulae, or dissection but also may occur spontaneously. Neonates may present with clubfoot and/or congenital dislocation of the hips. In childhood, inguinal hernia, pneumothorax, and recurrent joint subluxation or dislocation can occur. Pregnancy for women with EDS type IV has as much as a 12% risk for death from peripartum arterial rupture or uterine rupture. One-fourth of individuals with EDS type IV who have undergone laboratory testing to confirm their diagnosis have experienced a significant medical problem by age 20 years and more than 80% by age 40 years. The median age of death in this reviewed population was 48 years.
Cutis laxa, X-linked
MedGen UID:
82793
Concept ID:
C0268353
Congenital Abnormality
Menkes disease, occipital horn syndrome (OHS), and ATP7A-related distal motor neuropathy (DMN) are disorders of copper transport caused by mutations in the copper-transporting ATPase gene (ATP7A). Infants with classic Menkes disease appear healthy until age two to three months, when loss of developmental milestones, hypotonia, seizures, and failure to thrive occur. The diagnosis is usually suspected when infants exhibit typical neurologic changes and concomitant characteristic changes of the hair (short, sparse, coarse, twisted, and often lightly pigmented). Temperature instability and hypoglycemia may be present in the neonatal period. Death usually occurs by age three years. Occipital horn syndrome is characterized by "occipital horns," distinctive wedge-shaped calcifications at the sites of attachment of the trapezius muscle and the sternocleidomastoid muscle to the occipital bone. Occipital horns may be clinically palpable or observed on skull radiographs. Individuals with OHS also have lax skin and joints, bladder diverticula, inguinal hernias, and vascular tortuosity. Intellect is normal or slightly reduced. ATP7A-related distal motor neuropathy, an adult-onset disorder resembling Charcot-Marie-Tooth disease, shares none of the clinical or biochemical abnormalities characteristic of Menkes disease or OHS.
Cutis laxa-corneal clouding-oligophrenia syndrome
MedGen UID:
82794
Concept ID:
C0268354
Congenital Abnormality
De Barsy syndrome, or autosomal recessive cutis laxa type III (ARCL3), is characterized by cutis laxa, a progeria-like appearance, and ophthalmologic abnormalities (summary by Kivuva et al., 2008). Genetic Heterogeneity of De Barsy Syndrome Autosomal recessive cutis laxa type IIIA (ARCL3A) is caused by mutation in the ALDH18A1 gene. ARCL3B is caused by mutation in the PYCR1 gene (179035). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see 219200.
Deficiency of glycerol kinase
MedGen UID:
82803
Concept ID:
C0268418
Disease or Syndrome
Francke et al. (1987) noted that there are 3 clinically distinct forms of glycerol kinase deficiency: infantile, juvenile, and adult. The infantile form is associated with severe developmental delay, and those with the adult form have no symptoms and are often detected fortuitously. The infantile form of GK deficiency, or the 'GK complex,' results from the Xp21 contiguous gene deletion syndrome (300679) with congenital adrenal hypoplasia (300200) and/or Duchenne muscular dystrophy (DMD; 310200), whereas the juvenile and adult forms have isolated GK deficiency (Walker et al., 1996).
Alstrom syndrome
MedGen UID:
78675
Concept ID:
C0268425
Congenital Abnormality
Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated or restrictive cardiomyopathy, the insulin resistance syndrome, and multiple organ failure. Wide clinical variability is observed among affected individuals, even within the same family. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Progressive sensorineural hearing loss presents in the first decade in as many as 70% of individuals. Hearing loss may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to type 2 diabetes in the majority by the third decade. Nearly all demonstrate associated dyslipidemia. Other endocrine abnormalities can include hypothyroidism, hypogonadotropic hypogonadism in boys, and polycystic ovaries in girls. More than 60% of individuals with Alström syndrome develop cardiac failure as a result of dilated or restrictive cardiomyopathy. About 50% of individuals have delay in early developmental milestones; intelligence is normal. Liver involvement includes elevation of transaminases, steatosis, hepatosplenomegaly, and steatohepatitis. Portal hypertension and cirrhosis can lead to hepatic encephalopathy and life-threatening esophageal varices. Pulmonary dysfunction and severe renal disease may also develop. End-stage renal disease (ESRD) can occur as early as the late teens.
Dihydropteridine reductase deficiency
MedGen UID:
75682
Concept ID:
C0268465
Disease or Syndrome
Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature.
Tyrosinemia type 2
MedGen UID:
75687
Concept ID:
C0268487
Disease or Syndrome
Tyrosinemia type II is an autosomal recessive disorder characterized by keratitis, painful palmoplantar hyperkeratosis, mental retardation, and elevated serum tyrosine levels. The disorder is caused by deficiency of hepatic tyrosine aminotransferase (Natt et al., 1992).
Cross syndrome
MedGen UID:
82811
Concept ID:
C0268496
Congenital Abnormality
A syndrome of gingival fibromatosis, pigmentation disorders, microphthalmia, and delayed psychomotor development. It was first observed in the Kramer family, hence the synonym Kramer syndrome.
Prolidase deficiency
MedGen UID:
120647
Concept ID:
C0268532
Disease or Syndrome
Prolidase deficiency is a rare autosomal recessive multisystem disorder associated with massive imidodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. The disorder is clinically heterogeneous and severity varies widely. Features include chronic, slowly healing ulcerations, mainly on the legs and feet. The ulcers are often preceded by other dermatologic manifestations that may occur anywhere and include erythematous papular eruptions, telangiectasias with pruritus and photosensitivity, impetigo-like eruptions, pruritic eczematous lesions, and necrotic papules. Mild to severe mental retardation is often a feature, and recurrent respiratory tract infections, sometimes fatal, are common. Facial dysmorphism may include low hairline and hirsutism, saddle nose, ocular hypertelorism, micrognathia, a high-arched palate, mandibular protrusion, and exophthalmos. Clinical manifestations are usually detectable after birth or in early childhood, but late-onset cases have been reported (summary by Lupi et al., 2008).
Hyperammonemia, type III
MedGen UID:
120649
Concept ID:
C0268543
Disease or Syndrome
N-acetylglutamate synthase deficiency is an autosomal recessive disorder of the urea cycle. The clinical and biochemical features of the disorder are indistinguishable from carbamoyl phosphate synthase I deficiency (237300), since the CPS1 enzyme (608307) has an absolute requirement for NAGS (Caldovic et al., 2007).
Argininosuccinate lyase deficiency
MedGen UID:
78687
Concept ID:
C0268547
Disease or Syndrome
Deficiency of argininosuccinate lyase (ASL), the enzyme that cleaves argininosuccinic acid to produce arginine and fumarate in the fourth step of the urea cycle, is characterized by a severe neonatal onset form and a late onset form. The severe neonatal onset form, which is indistinguishable from that of other urea cycle disorders, is characterized by hyperammonemia within the first few days after birth accompanied by vomiting, lethargy, hypothermia, and poor feeding. In the absence of treatment, lethargy, seizures, and coma worsen, resulting in death. In contrast, the late onset form ranges from episodic hyperammonemia triggered by acute infection or stress to cognitive impairment, behavioral abnormalities, and/or learning disabilities in the absence of any documented episodes of hyperammonemia. Manifestations of ASL deficiency that appear to be unrelated to the severity or duration of hyperammonemic episodes include: (1) neurocognitive deficiencies (attention deficit hyperactivity disorder [ADHD], developmental disability, seizures, and learning disability); (2) liver disease (hepatitis, cirrhosis); (3) trichorrhexis nodosa (coarse brittle hair that breaks easily); and (4) systemic hypertension.
Arginase deficiency
MedGen UID:
78688
Concept ID:
C0268548
Disease or Syndrome
Arginase deficiency in untreated individuals is characterized by episodic hyperammonemia of variable degree that is infrequently severe enough to be life threatening or to cause death. Most commonly, birth and early childhood are normal. Untreated individuals have slowing of linear growth at age one to three years, followed by development of spasticity, plateauing of cognitive development, and subsequent loss of developmental milestones. If untreated, arginase deficiency usually progresses to severe spasticity, loss of ambulation, complete loss of bowel and bladder control, and severe intellectual disability. Seizures are common and are usually controlled easily.
Hyperlysinemia
MedGen UID:
82816
Concept ID:
C0268553
Disease or Syndrome
Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant (summary by Tondo et al., 2013; Houten et al., 2013). The AASS gene encodes a bifunctional enzyme: lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase. In hyperlysinemia type I, both enzymatic functions of AASS are defective; in hyperlysinemia type II, also known as saccharopinuria (268700), some of the first enzymatic function is retained (Cox, 1985; Cox et al., 1985).
Isovaleryl-CoA dehydrogenase deficiency
MedGen UID:
82822
Concept ID:
C0268575
Disease or Syndrome
The term "organic acidemia" or "organic aciduria" (OA) applies to a group of disorders characterized by the excretion of non-amino organic acids in urine. Most organic acidemias result from dysfunction of a specific step in amino acid catabolism, usually the result of deficient enzyme activity. The majority of the classic organic acid disorders are caused by abnormal amino acid catabolism of branched-chain amino acids or lysine. They include maple syrup urine disease (MSUD), propionic acidemia, methylmalonic acidemia (MMA), methylmalonic aciduria and homocystinuria, isovaleric acidemia, biotin-unresponsive 3-methylcrotonyl-CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency, ketothiolase deficiency, and glutaricacidemia type I (GA I). A neonate affected with an OA is usually well at birth and for the first few days of life. The usual clinical presentation is that of toxic encephalopathy and includes vomiting, poor feeding, neurologic symptoms such as seizures and abnormal tone, and lethargy progressing to coma. Outcome is enhanced by diagnosis and treatment in the first ten days of life. In the older child or adolescent, variant forms of the OAs can present as loss of intellectual function, ataxia or other focal neurologic signs, Reye syndrome, recurrent ketoacidosis, or psychiatric symptoms.
Propionic acidemia
MedGen UID:
75694
Concept ID:
C0268579
Disease or Syndrome
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. Neonatal-onset PA, the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, coma, and death. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Late-onset PA includes developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction (resulting in dystonia and choreoathetosis) and cardiomyopathy. Affected children can have an acute decompensation that resembles the neonatal presentation and is precipitated by a catabolic stress such as infection, injury, or surgery. Isolated cardiomyopathy and arrhythmia can be observed on rare occasion in the absence of clinical metabolic decompensation or neurocognitive deficits. Manifestations of neonatal and late-onset PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency (POI), and chronic renal failure.
Glutaric aciduria, type 1
MedGen UID:
124337
Concept ID:
C0268595
Disease or Syndrome
The term "organic acidemia" or "organic aciduria" (OA) applies to a group of disorders characterized by the excretion of non-amino organic acids in urine. Most organic acidemias result from dysfunction of a specific step in amino acid catabolism, usually the result of deficient enzyme activity. The majority of the classic organic acid disorders are caused by abnormal amino acid catabolism of branched-chain amino acids or lysine. They include maple syrup urine disease (MSUD), propionic acidemia, methylmalonic acidemia (MMA), methylmalonic aciduria and homocystinuria, isovaleric acidemia, biotin-unresponsive 3-methylcrotonyl-CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency, ketothiolase deficiency, and glutaricacidemia type I (GA I). A neonate affected with an OA is usually well at birth and for the first few days of life. The usual clinical presentation is that of toxic encephalopathy and includes vomiting, poor feeding, neurologic symptoms such as seizures and abnormal tone, and lethargy progressing to coma. Outcome is enhanced by diagnosis and treatment in the first ten days of life. In the older child or adolescent, variant forms of the OAs can present as loss of intellectual function, ataxia or other focal neurologic signs, Reye syndrome, recurrent ketoacidosis, or psychiatric symptoms.
Succinate-semialdehyde dehydrogenase deficiency
MedGen UID:
124340
Concept ID:
C0268631
Disease or Syndrome
Succinic semialdehyde dehydrogenase (SSADH) deficiency is characterized by psychomotor retardation, childhood-onset hypotonia, and ataxia. Seizures occur in more than 50% of affected individuals. Hyperkinetic behavior, aggression, self-injurious behaviors, hallucinations, and sleep disturbances have been reported in nearly half of all patients, and are common in older individuals. Basal ganglia signs such as choreoathetosis, dystonia, and myoclonus have been reported in a few individuals with earlier-onset, more severe disease. Involvement beyond the central nervous system has not been described.
Histidine transport defect
MedGen UID:
82825
Concept ID:
C0268642
Congenital Abnormality
Alexander's disease
MedGen UID:
78724
Concept ID:
C0270726
Disease or Syndrome
Alexander disease is a progressive disorder of cerebral white matter that predominantly affects infants and children and has variable life expectancy. The later-onset forms present with a slower clinical course. The infantile form comprises about 42% of affected individuals, the juvenile form about 22%, and the adult form about 33%. A neonatal form is also recognized. The neonatal form leads to severe disability or death within two years. Characteristics include seizures, hydrocephalus, severe motor and intellectual disability, and elevated CSF protein concentration. MRI shows severe white matter abnormalities with involvement of the basal ganglia and cerebellum. The infantile form presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly, frontal bossing, and seizures. Other findings include hyperreflexia and pyramidal signs, ataxia, and occasional hydrocephalus secondary to aqueductal stenosis. Affected children survive weeks to several years. The juvenile form usually presents between ages four and ten years, occasionally in the mid-teens. Findings can include bulbar/pseudobulbar signs, ataxia, gradual loss of intellectual function, seizures, normocephaly or megalencephaly, and breathing problems. Survival ranges from the early teens to the 20s-30s. The adult form is the most variable.
Laron-type isolated somatotropin defect
MedGen UID:
78776
Concept ID:
C0271568
Disease or Syndrome
Laron syndrome is an autosomal recessive disorder characterized by marked short stature that results from failure to generate insulin-like growth factor I (IGF1; 147440) in response to growth hormone (GH; 139250). GH levels are normal or increased. The disorder is caused by dysfunction of the growth hormone receptor. A Laron syndrome-like phenotype associated with immunodeficiency (245590) is caused by postreceptor defect, i.e. mutation in the STAT5B gene (604260). Patients with mutations in the GHR gene that cause only partial insensitivity to growth hormone have a form of short stature (604271).
Pendred's syndrome
MedGen UID:
82890
Concept ID:
C0271829
Congenital Abnormality
Pendred syndrome (PDS) and DFNB4 comprise a phenotypic spectrum of hearing loss with or without other findings. Pendred syndrome is characterized by: severe-to-profound bilateral sensorineural hearing impairment that is usually congenital (or prelingual) and non-progressive; vestibular dysfunction; temporal bone abnormalities; and development of euthyroid goiter in late childhood to early adulthood. Variability of findings is considerable, even within the same family. DFNB4 is characterized by nonsyndromic sensorineural hearing impairment, vestibular dysfunction, and enlarged vestibular aqueduct (EVA). Thyroid defects are not seen in DFNB4.
Shwachman syndrome
MedGen UID:
124418
Concept ID:
C0272170
Disease or Syndrome
Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multi-lineage cytopenias and susceptibility to myelodysplasia syndrome (MDS) and acute myelogeneous leukemia (AML); and bone abnormalities. In almost all affected children, persistent or intermittent neutropenia is a common presenting finding, often before the diagnosis of SDS is made. Short stature and recurrent infections are common.
Septo-optic dysplasia sequence
MedGen UID:
90926
Concept ID:
C0338503
Congenital Abnormality
Septooptic dysplasia is a clinically heterogeneous disorder loosely defined by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum (Dattani et al., 1998). The diagnosis of this rare congenital anomaly is made when 2 or more features of the classic triad are present. Approximately 30% of patients have complete manifestations, 62% display hypopituitarism, and 60% have an absent septum pellucidum. The disorder is equally prevalent in males and females and is more common in infants born to younger mothers, with a reported incidence of 1 in 10,000 live births (summary by Webb and Dattani, 2010). Also see 516020.0012 for a form of septooptic dysplasia associated with cardiomyopathy and exercise intolerance.
Capillary malformations, congenital, 1
MedGen UID:
90955
Concept ID:
C0340803
Congenital Abnormality
Capillary malformations are a form of vascular malformation that are present from birth, tend to grow with the individual, do not regress spontaneously, and show normal rates of endothelial cell turnover. Capillary malformations are distinct from capillary hemangiomas (602089), which are highly proliferative lesions that appear shortly after birth and show rapid growth, slow involution, and endothelial hypercellularity (Spring and Bentz, 2005; Legiehn and Heran, 2006).
Fetal iodine deficiency disorder
MedGen UID:
83336
Concept ID:
C0342200
Disease or Syndrome
Severely reduced physical and mental growth associated with pyramidal and extrapyramidal signs and symptoms, due to dietary iodine deficiency.
Bird-headed dwarfism with progressive ataxia, insulin-resistant diabetes, goiter, and primary gonadal insufficiency
MedGen UID:
90978
Concept ID:
C0342284
Congenital Abnormality
Hypogonadism, diabetes mellitus, alopecia, mental retardation and electrocardiographic abnormalities
MedGen UID:
83337
Concept ID:
C0342286
Congenital Abnormality
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. Ten types and their associated genes are recognized. The age of onset ranges from infancy to late adulthood; the rate of progression varies. Cognitive decline occurs in some subtypes, but more often cognition is relatively spared. Cerebellar atrophy is a frequent finding in some subtypes.
Klein-Waardenberg's syndrome
MedGen UID:
449531
Concept ID:
C0342680
Disease or Syndrome
Waardenburg syndrome type 3 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; presence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi; and upper limb abnormalities (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 3 is also referred to as 'Klein-Waardenburg syndrome' (Gorlin et al., 1976). Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type IV (WS4; 277580), also known as Waardenburg-Shah syndrome, has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010).
Congenital defect of folate absorption
MedGen UID:
83348
Concept ID:
C0342705
Disease or Syndrome
Hereditary folate malabsorption (HFM) is characterized by folate deficiency with impaired intestinal folate absorption and impaired folate transport into the central nervous system (CNS). Findings include poor feeding and failure to thrive, anemia often accompanied by leukopenia and/or thrombocytopenia, diarrhea and/or oral mucositis, hypoimmunoglobulinemia, and other immunologic dysfunction resulting in infections with unusual organisms. Neurologic manifestations include developmental delays, cognitive and motor impairment, behavioral disorders and, frequently, seizures.
3-Methylglutaconic aciduria
MedGen UID:
90994
Concept ID:
C0342727
Disease or Syndrome
3-methylglutaconyl-CoA hydratase deficiency is an inherited condition that causes neurological problems. Beginning in infancy to early childhood, children with this condition often have delayed development of mental and motor skills (psychomotor delay), speech delay, involuntary muscle cramping (dystonia), and spasms and weakness of the arms and legs (spastic quadriparesis). Affected individuals can also have optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain. In some cases, signs and symptoms of 3-methylglutaconyl-CoA hydratase deficiency begin in adulthood, often in a person's twenties or thirties. These individuals have damage to a type of brain tissue called white matter (leukoencephalopathy), which likely contributes to progressive problems with speech (dysarthria), difficulty coordinating movements (ataxia), stiffness (spasticity), optic atrophy, and a decline in intellectual function (dementia). Affected individuals who show symptoms of 3-methylglutaconyl-CoA hydratase deficiency in childhood often go on to develop leukoencephalopathy and other neurological problems in adulthood. All people with 3-methylglutaconyl-CoA hydratase deficiency accumulate large amounts of a substance called 3-methylglutaconic acid in their body fluids. As a result, they have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria). 3-methylglutaconyl-CoA hydratase deficiency is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with 3-methylglutaconyl-CoA hydratase deficiency also have high urine levels of another acid called 3-methylglutaric acid.
Deficiency of malonyl-CoA decarboxylase
MedGen UID:
91001
Concept ID:
C0342793
Disease or Syndrome
Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001).
Beta-D-mannosidosis
MedGen UID:
87462
Concept ID:
C0342849
Disease or Syndrome
Beta-mannosidosis is an autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of lysosomal beta-mannosidase activity. The most severely affected patients show developmental delay and mental retardation, but there are differing levels of severity and some patients may have comparatively mild disease (Bedilu et al., 2002) The disorder was first described in goats (Jones and Dawson, 1981), who have a more severe neurodegenerative disorder than that seen in humans.
Gorlin-Chaudhry-Moss syndrome
MedGen UID:
87500
Concept ID:
C0345382
Disease or Syndrome
Congenital livedo reticularis
MedGen UID:
83381
Concept ID:
C0345419
Congenital Abnormality
Carbohydrate-deficient glycoprotein syndrome type II
MedGen UID:
87610
Concept ID:
C0349654
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Congenital laryngeal abductor palsy
MedGen UID:
96004
Concept ID:
C0396059
Congenital Abnormality
Laryngeal abductor paralysis with inspiratory stridor, swallowing difficulty, asphyxia, and mental deficiency. Adductor laryngeal paralysis (OMIM 150270) is a variant in which hoarseness from birth appears to be the only symptom. Terms familial vocal cord dysfunction and laryngeal abductor paralysis are also used as the synonyms for the Plott syndrome which is transmitted as an X-linked trait.
Hyperimmunoglobulin D with periodic fever
MedGen UID:
140768
Concept ID:
C0398691
Disease or Syndrome
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often. Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA). During episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. A small number of people with HIDS have intellectual disability, problems with movement and balance (ataxia), eye problems, and recurrent seizures (epilepsy). Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why people with HIDS have high levels of IgD and IgA. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy. People with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, progressive ataxia, progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy.
Microcephaly, normal intelligence and immunodeficiency
MedGen UID:
140771
Concept ID:
C0398791
Congenital Abnormality
Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, intrauterine growth retardation and short stature, recurrent sinopulmonary infections, an increased risk for cancer, and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time and most children tested after age seven years have mild to moderate intellectual disability. Recurrent pneumonia and bronchitis may result in respiratory failure and early death. Approximately 40% of affected individuals have developed malignancies before age 20 years, with the risk being highest for T-cell (55%) and B-cell lymphomas (45%). Other tumors include T-cell lymphoma and solid tumors (e.g., medulloblastoma, glioma, and rhabdomyosarcoma). Note, however, that much of what is reported about NBS is based on individuals who are homozygous for the single most common Eastern European pathogenic variant, 657_661del5.
Metageria
MedGen UID:
96063
Concept ID:
C0406584
Disease or Syndrome
Neonatal pseudo-hydrocephalic progeroid syndrome
MedGen UID:
140806
Concept ID:
C0406586
Disease or Syndrome
The neonatal progeroid syndrome, also known as Wiedemann-Rautenstrauch syndrome, is a rare autosomal recessive disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, hypotonia, variable mental impairment, and death in childhood (summary by Toriello, 1990).
Wrinkly skin syndrome
MedGen UID:
98030
Concept ID:
C0406587
Disease or Syndrome
ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), spans a phenotypic spectrum that includes Debré-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end. Affected individuals have furrowing of the skin of the whole body that improves with time. They may have other evidence of a generalized connective disorder, including enlarged anterior fontanelle in infancy, congenital dislocation of the hips, inguinal hernias, and high myopia. In most (not all) affected individuals, cortical and cerebellar malformations are present and are associated with severe developmental delays, seizures, and neurologic regression.
Encephalocraniocutaneous lipomatosis
MedGen UID:
140807
Concept ID:
C0406612
Congenital Abnormality
Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies (Moog et al., 2007).
Odontotrichomelic syndrome
MedGen UID:
98034
Concept ID:
C0406723
Congenital Abnormality
The GAPO syndrome is the acronymic designation for a complex of growth retardation, alopecia, pseudoanodontia (failure of tooth eruption), and progressive optic atrophy (Tipton and Gorlin, 1984). Ilker et al. (1999) noted that optic atrophy is not a consistent feature of this disorder.
Trichodental syndrome
MedGen UID:
96068
Concept ID:
C0406724
Congenital Abnormality
Orofacial-digital syndrome III
MedGen UID:
96069
Concept ID:
C0406726
Congenital Abnormality
Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes). Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder. The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability. Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums. Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism). Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome. Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.
Orofacial-digital syndrome IV
MedGen UID:
98358
Concept ID:
C0406727
Congenital Abnormality
Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes). Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder. The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability. Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums. Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism). Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome. Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.
Chronic infantile neurological, cutaneous and articular syndrome
MedGen UID:
98370
Concept ID:
C0409818
Disease or Syndrome
Chronic infantile neurologic cutaneous and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central nervous system involvement, and arthropathy (Feldmann et al., 2002). See also familial cold autoinflammatory syndrome-1 (FCAS1, CAPS1; 120100), an allelic disorder with a less severe phenotype.
Hypochondroplasia
MedGen UID:
98376
Concept ID:
C0410529
Congenital Abnormality
Hypochondroplasia is a skeletal dysplasia characterized by short stature; stocky build; disproportionately short arms and legs; broad, short hands and feet; mild joint laxity; and macrocephaly. Radiologic features include shortening of long bones with mild metaphyseal flare; narrowing of the inferior lumbar interpedicular distances; short, broad femoral neck; and squared, shortened ilia. The skeletal features are very similar to those seen in achondroplasia but tend to be milder. Medical complications common to achondroplasia (e.g., spinal stenosis, tibial bowing, obstructive apnea) occur less frequently in hypochondroplasia but intellectual disability and epilepsy may be more prevalent. Children usually present as toddlers or school-age children with decreased growth velocity leading to short stature and limb disproportion. Other features also become more prominent over time.
Aniridia, cerebellar ataxia, and mental retardation
MedGen UID:
96563
Concept ID:
C0431401
Disease or Syndrome
Gillespie syndrome is a disorder that involves eye abnormalities, problems with balance and coordinating movements (ataxia), and mild to moderate intellectual disability. Gillespie syndrome is characterized by aniridia, which is the absence of the colored part of the eye (the iris). In most affected individuals, only part of the iris is missing (partial aniridia) in both eyes, but in some affected individuals, partial aniridia affects only one eye, or the entire iris is missing (complete aniridia) in one or both eyes. The absence of all or part of the iris can cause blurry vision (reduced visual acuity) and increased sensitivity to light (photophobia). Rapid, involuntary eye movements (nystagmus) can also occur in Gillespie syndrome. The balance and movement problems in Gillespie syndrome result from underdevelopment (hypoplasia) of a part of the brain called the cerebellum. This abnormality can cause delayed development of motor skills such as walking. In addition, difficulty controlling the muscles in the mouth can lead to delayed speech development. The difficulties with coordination generally become noticeable in early childhood when the individual is learning these skills. People with Gillespie syndrome usually continue to have an unsteady gait and speech problems. However, the problems do not get worse over time, and in some cases they improve slightly. Other features of Gillespie syndrome can include abnormalities in the bones of the spine (vertebrae) and malformations of the heart.
Asymmetric crying face association
MedGen UID:
140911
Concept ID:
C0431406
Congenital Abnormality
22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2. 22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. Common signs and symptoms include heart abnormalities that are often present from birth, an opening in the roof of the mouth (a cleft palate), and distinctive facial features. People with 22q11.2 deletion syndrome often experience recurrent infections caused by problems with the immune system, and some develop autoimmune disorders such as rheumatoid arthritis and Graves disease in which the immune system attacks the body's own tissues and organs. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones. Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and learning disabilities. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia, depression, anxiety, and bipolar disorder. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention deficit hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorders that affect communication and social interaction. Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.
Familial hypoplastic, glomerulocystic kidney
MedGen UID:
96569
Concept ID:
C0431693
Congenital Abnormality
The 'renal cysts and diabetes syndrome' is an autosomal dominant disorder comprising (1) nondiabetic renal disease resulting from abnormal renal development, and (2) diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelvises, abnormal calyces, small kidney, single kidney, horseshoe kidney, and hyperuricemic nephropathy. Affected individuals may also have abnormalities of the genital tract, including vaginal aplasia, rudimentary uterus, bicornuate uterus, epididymal cysts, and atresia of the vas deferens (Bingham et al., 2001; Fajans et al., 2001; Bellanne-Chantelot et al., 2004; Edghill et al., 2006). The renal abnormalities seen in the RCAD syndrome are part of a spectrum of malformations known as congenital anomalies of the kidney and urinary tract (CAKUT; see 610805) (summary by Nakayama et al., 2010).
Adducted thumbs syndrome
MedGen UID:
98140
Concept ID:
C0431886
Congenital Abnormality
Wolcott-Rallison dysplasia
MedGen UID:
140926
Concept ID:
C0432217
Congenital Abnormality
Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis, and growth retardation develop at a later age. Other frequent multisystem manifestations include hepatic and renal dysfunction, mental retardation, and cardiovascular abnormalities (summary by Delepine et al., 2000).
Nievergelt's syndrome
MedGen UID:
98478
Concept ID:
C0432231
Disease or Syndrome
Spondyloepimetaphyseal dysplasia with joint laxity
MedGen UID:
98148
Concept ID:
C0432243
Congenital Abnormality
Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) is characterized by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis, thoracic asymmetry, and respiratory compromise resulting in early death. Nonaxial skeletal involvement includes elbow deformities with radial head dislocation, dislocated hips, clubfeet, and tapered fingers with spatulate distal phalanges. Many affected children have an oval face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Palatal abnormalities and congenital heart disease are also observed (summary by Smith et al., 1999). Patients with a similar phenotype and fractures have been described (Malfait et al., 2013).
Osteoporosis with pseudoglioma
MedGen UID:
98480
Concept ID:
C0432252
Disease or Syndrome
Osteoporosis-pseudoglioma syndrome is a rare condition characterized by severe thinning of the bones (osteoporosis) and eye abnormalities that lead to vision loss. In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes). Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye (the retina), although other eye conditions have been identified in affected individuals. Pseudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma. Rarely, people with osteoporosis-pseudoglioma syndrome have additional signs or symptoms such as mild intellectual disability, weak muscle tone (hypotonia), abnormally flexible joints, or seizures.
Geroderma osteodysplastica
MedGen UID:
98149
Concept ID:
C0432255
Disease or Syndrome
Dysosteosclerosis
MedGen UID:
98150
Concept ID:
C0432262
Disease or Syndrome
Dysosteosclerosis is a rare bone dysplasia associated with neurodevelopmental deterioration. There is sclerosis and platyspondyly with progressive metaphyseal expansion and alteration of bone density. The early craniotubular bone modeling and clinical presentation resemble osteopetrosis (summary by Elcioglu et al., 2002).
Osteopathia striata with cranial sclerosis
MedGen UID:
96590
Concept ID:
C0432268
Disease or Syndrome
Osteopathia striata with cranial sclerosis is an X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae (Jenkins et al., 2009). In males, the disorder is usually associated with fetal or neonatal lethality. Occasional surviving males have, in addition to hyperostosis, cardiac, intestinal, and genitourinary malformations. Osteosclerosis in the cranial and facial bones leads to disfigurement and to disability due to pressure on cranial nerves, e.g., deafness. Osteopathia striata is a frequent feature of focal dermal hypoplasia (FDH; 305600). Although early reports of familial cases of this disorder appeared to suggest autosomal dominant inheritance (see, e.g., Horan and Beighton, 1978 and Konig et al., 1996), reappraisal of the literature (Behninger and Rott, 2000; Rott et al., 2003) and the finding of a molecular basis for the disorder by Jenkins et al. (2009) confirms that the inheritance pattern is X-linked dominant. Affected males who survive have a more severe phenotype than affected females, and sporadic male cases may result from somatic mosaicism (Behninger and Rott, 2000).
Lenz-Majewski hyperostosis syndrome
MedGen UID:
98483
Concept ID:
C0432269
Disease or Syndrome
Lenz-Majewski hyperostotic dwarfism is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, distinct craniofacial and dental anomalies, loose skin, and distal limb anomalies, particularly brachydactyly and symphalangism. Patients have multiple radiographic abnormalities due to progressive generalized hyperostosis that affects the cranium, vertebrae, and diaphyses of tubular bones, leading to severe growth retardation (summary by Sousa et al., 2014).
Osteoglophonic dysplasia
MedGen UID:
96592
Concept ID:
C0432283
Congenital Abnormality
Osteoglophonic dysplasia is a condition characterized by abnormal bone growth that leads to severe head and face (craniofacial) abnormalities, dwarfism, and other features. The term osteoglophonic refers to the bones (osteo-) having distinctive hollowed out (-glophonic) areas that appear as holes on x-ray images. Premature fusion of certain bones in the skull (craniosynostosis) typically occurs in osteoglophonic dysplasia. The craniosynostosis associated with this disorder may give the head a tall appearance, often referred to in the medical literature as a tower-shaped skull, or a relatively mild version of a deformity called a cloverleaf skull. Characteristic facial features in people with osteoglophonic dysplasia include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), a large tongue (macroglossia), a protruding jaw (prognathism), and a short neck. People with this condition usually have no visible teeth because the teeth never emerge from the jaw (clinical anodontia). In addition, the gums are often overgrown (hypertrophic gingiva). Infants with osteoglophonic dysplasia often experience failure to thrive, which means they do not gain weight and grow at the expected rate. Affected individuals have short, bowed legs and arms and are short in stature. They also have flat feet and short, broad hands and fingers. The life expectancy of people with osteoglophonic dysplasia depends on the extent of their craniofacial abnormalities; those that obstruct the air passages and affect the mouth and teeth can lead to respiratory problems and cause difficulty with eating and drinking. Despite the skull abnormalities, intelligence is generally not affected in this disorder.
Deletion of short arm of chromosome 18
MedGen UID:
96604
Concept ID:
C0432442
Disease or Syndrome
Deletion of the short arm of chromosome 18. It is one of the most fre quently occurring chromosomal aberrations with minimal abnormalities visible at birth, which become more apparent at the age of three years. The phenotype is marked mainly by holoprosencephaly, brachycephaly, broad facies, blepharoptosis, downturned corners of the mouth, tooth abnormalities, broad neck with low posterior hairline, funnel chest, enlarged labia majora, hand abnormalities, mental retardation ranging from mild to severe, and other malformations. The phenotype varies from case to case, frequently reflecting the length and type of deletion: del(18p) mosaicism is associated with abnormalities which are similar to those in del(18p) and include microphthalmia and cataract and cyclopia may occur in del(18p) in mosaicism with dup(18p).
Michelin-tire baby
MedGen UID:
96881
Concept ID:
C0473586
Disease or Syndrome
Symmetric ringed creases around the extremities which disappear later in life. They are reminiscent of these of the mascot of the tire manufacturer, Michelin, hence the name of the syndrome. Associated abnormalities vary and may include facial dysmorphism, upslanting palpebral fissures, hypertelorism, cleft palate, genital anomalies, mild developmental delay, ureterocele, smooth muscle hamartoma, nevus lipomatosus, Laron syndrome (dwarfism and high growth hormone and low somatomedin activity), and other defects.
Neurocutaneous melanosis
MedGen UID:
154259
Concept ID:
C0544862
Pathologic Function
Neurocutaneous melanosis, or neuromelanosis, is characterized by the presence of melanin-producing cells within the brain parenchyma or leptomeninges, which may lead to clinically apparent neurologic signs and symptoms, such as seizures. Other neurologic abnormalities, including hydrocephalus, arachnoid cysts, tumors, and syringomyelia, may also occur. The disorder is a rare but severe manifestation of congenital melanocytic nevus syndrome (CMNS; 137550). Some patients with neurocutaneous melanosis or CMNS may develop malignant melanoma. The incidence of neurologic involvement, development of malignant melanoma, and death is significantly associated with the projected adult size of the largest congenital melanocytic nevus, particularly those greater than 40 cm (summary by Kinsler et al., 2008; Kinsler et al., 2013).
Beaded hair
MedGen UID:
108185
Concept ID:
C0546966
Congenital Abnormality
Individuals with monilethrix have normal hair at birth, but within the first few months of life develop fragile, brittle hair that tends to fracture and produce varying degrees of dystrophic alopecia. In the mildest forms, only the occipital regions of the scalp are involved; however, in severe forms the eyebrows, eyelashes, and secondary sexual hair may also be involved. Follicular hyperkeratosis with predilection for the scalp, nape of neck, and extensor surfaces of the upper arm and thighs is also a characteristic finding in these patients. Light microscopic examination is diagnostic and reveals elliptical nodes of normal thickness and intermittent constrictions (internodes) at which the hair easily breaks. There may be spontaneous improvement with time, especially during puberty and pregnancy, but the condition never resolves completely (summary by Zlotogorski et al., 2006). An autosomal recessive form of monilethrix-like congenital hypotrichosis (see 607903) is caused by mutation in the DSG4 gene (607892). The clinical picture of autosomal recessive monilethrix is more severe than the dominant form, with more extensive alopecia of the scalp, body, and limbs, and a papular rash involving the extremities and periumbilical region (Zlotogorski et al., 2006). The term monilethrix derives from the Latin word for necklace and the Greek for hair (Schweizer, 2006).
3-Methylglutaconic aciduria type 3
MedGen UID:
108273
Concept ID:
C0574084
Disease or Syndrome
OPA3-related 3-methylglutaconic aciduria is characterized by optic atrophy and/or choreoathetoid movement disorder with onset before age ten years. Optic atrophy is associated with progressive, decreased visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus. Most individuals have chorea, often severe enough to restrict ambulation. Some are confined to a wheelchair from an early age. Although most individuals develop spastic paraparesis, mild ataxia, and occasional mild cognitive deficit in their second decade, the course of the disease is relatively stable.
Costello syndrome
MedGen UID:
108454
Concept ID:
C0587248
Disease or Syndrome
Costello syndrome is characterized by failure to thrive in infancy as a result of severe postnatal feeding difficulties; short stature; developmental delay or intellectual disability; coarse facial features (full lips, large mouth, full nasal tip); curly or sparse, fine hair; loose, soft skin with deep palmar and plantar creases; papillomata of the face and perianal region; diffuse hypotonia and joint laxity with ulnar deviation of the wrists and fingers; tight Achilles tendons; and cardiac involvement including: cardiac hypertrophy (usually typical hypertrophic cardiomyopathy [HCM]), congenital heart defect (usually valvar pulmonic stenosis), and arrhythmia (usually supraventricular tachycardia, especially chaotic atrial rhythm/multifocal atrial tachycardia or ectopic atrial tachycardia). Relative or absolute macrocephaly is typical, and postnatal cerebellar overgrowth can result in the development of a Chiari I malformation with associated anomalies including hydrocephalus or syringomyelia. Individuals with Costello syndrome have an approximately 15% lifetime risk for malignant tumors including rhabdomyosarcoma and neuroblastoma in young children and transitional cell carcinoma of the bladder in adolescents and young adults.
Aglossia-adactyly syndrome
MedGen UID:
108567
Concept ID:
C0595985
Congenital Abnormality
Hypoglossia-hypodactyly syndrome is characterized by a hypoplastic mandible, absence of the lower incisors, hypoglossia, and a variable degree of absence of the digits and limbs. Intelligence is normal (Hall, 1971). Hall (1971) classified what he termed the 'syndromes of oromandicular and limb hypogenesis,' which comprised a range of disorders with hypoglossia in common. Type I included hypoglossia and aglossia in isolation. Type II included hypoglossia with hypomelia/ hypodactylia. Type III included glossopalatine ankylosis with hypoglossia or hypoglossia and hypomelia/hypodactyly. Type IV included intraoral bands with fusion with hypoglossia or hypoglossia and hypomelia/hypodactyly. Type V included several syndromes, such as Hanhart syndrome, Pierre Robin syndrome (261800), Moebius syndrome (157900), and amniotic band syndrome (217100). Hall (1971) noted that complete aglossia or adactylia had not been reported, and suggested that 'hypoglossia-hypodactylia' is a more accurate term. See also hypoglossia and situs inversus (612776).
Anophthalmos with limb anomalies
MedGen UID:
154638
Concept ID:
C0599973
Congenital Abnormality
Ophthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. The features of this condition are present from birth. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). Usually both eyes are similarly affected in this condition, but if only one eye is small or missing, the other eye may have a defect such as a gap or split in its structures (coloboma). The most common hand and foot malformation seen in ophthalmo-acromelic syndrome is missing fingers or toes (oligodactyly). Other frequent malformations include fingers or toes that are fused together (syndactyly) or extra fingers or toes (polydactyly). These skeletal malformations are often described as acromelic, meaning that they occur in the bones that are away from the center of the body. Additional skeletal abnormalities involving the long bones of the arms and legs or the spinal bones (vertebrae) can also occur. Affected individuals may have distinctive facial features, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), or intellectual disability.
Gonadal dysgenesis with auditory dysfunction, autosomal recessive inheritance
MedGen UID:
151934
Concept ID:
C0685838
Congenital Abnormality
Perrault syndrome is a sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement (summary by Pierce et al., 2010). Pierce et al. (2010) noted that clinical heterogeneity of Perrault syndrome has prompted classification into type I, which is static and without neurologic disease, and type II, which is with progressive neurologic disease. Genetic Heterogeneity of Perrault Syndrome See also PRLTS2 (614926), caused by mutation in the HARS2 gene (600783) on chromosome 5q31; PRLTS3 (614129), caused by mutation in the CLPP gene (601119) on chromosome 19p13; PRLTS4 (615300), caused by mutation in the LARS2 gene (604544) on chromosome 3p21; and PRLTS5 (616138), caused by mutation in the C10ORF2 gene (606075) on chromosome 10q24.
Floating-Harbor syndrome
MedGen UID:
152667
Concept ID:
C0729582
Disease or Syndrome
Floating-Harbor syndrome (FHS) is characterized by typical craniofacial features; low birth weight, normal head circumference, and short stature; bone age delay that normalizes between ages six and 12 years; skeletal anomalies (brachydactyly, clubbing, clinodactyly, short thumbs, prominent joints, clavicular abnormalities); severe receptive and expressive language impairment; hypernasality and high-pitched voice; and intellectual disability that is typically mild to moderate. Difficulties with temperament and behavior that are present in many children tend to improve in adulthood. Other features can include: hyperopia and/or strabismus; conductive hearing loss; seizures; gastroesophageal reflux; renal anomalies (e.g., hydronephrosis/renal pelviectasis, cysts, and/or agenesis) and genital anomalies (e.g., hypospadias and/or undescended testes).
UDPglucose-4-epimerase deficiency
MedGen UID:
199598
Concept ID:
C0751161
Disease or Syndrome
Epimerase deficiency galactosemia (GALE deficiency galactosemia) is a continuum comprising three forms: Generalized. Enzyme activity is profoundly decreased in all tissues tested. Peripheral. Enzyme activity is deficient in red blood cells and circulating white blood cells, but normal or near normal in all other tissues. Intermediate. Enzyme activity is deficient in red blood cells and circulating white blood cells and less than 50% of normal levels in other cells tested. Infants with generalized epimerase deficiency galactosemia develop clinical findings on a regular milk diet (which contains lactose, a disaccharide of galactose and glucose); in contrast, neonates with the peripheral or intermediate form generally remain clinically well even on a regular milk diet and are usually only identified by biochemical testing, often in newborn screening programs. Because of the limited number of affected individuals reported to date, information on the natural history of all forms of epimerase deficiency galactosemia is limited. Infants with the profound generalized form who are on a diet containing galactose/lactose manifest hypotonia, poor feeding, vomiting, weight loss, jaundice, hepatomegaly, liver dysfunction, aminoaciduria, and cataracts. Prompt removal of galactose/lactose from their diet resolves or prevents these acute symptoms.
Lymphangiomyomatosis
MedGen UID:
148366
Concept ID:
C0751674
Neoplastic Process
Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body. LAM is found almost exclusively in women. It usually occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM. Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax). The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation. Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas.
Spinocerebellar ataxia 1
MedGen UID:
155703
Concept ID:
C0752120
Disease or Syndrome
Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. Early in the disease, affected individuals may have gait disturbance, slurred speech, difficulty with balance, brisk deep tendon reflexes, hypermetric saccades, nystagmus, and mild dysphagia. Later signs include slowing of saccadic velocity, development of up-gaze palsy, dysmetria, dysdiadochokinesia, and hypotonia. In advanced stages, muscle atrophy, decreased deep tendon reflexes, loss of proprioception, cognitive impairment (e.g., frontal executive dysfunction, impaired verbal memory), chorea, dystonia, and bulbar dysfunction are seen. Onset is typically in the third or fourth decade, although childhood onset and late adult onset have been reported. Those with onset over age 60 years may manifest a pure cerebellar phenotype. Interval from onset to death varies from ten to 30 years; individuals with juvenile onset show more rapid progression and more severe disease. Anticipation is observed. An axonal sensory neuropathy detected by electrophysiologic testing is common; brain imaging typically shows cerebellar and brain stem atrophy.
Potassium aggravated myotonia
MedGen UID:
156269
Concept ID:
C0752355
Disease or Syndrome
In a report on the 37th ENMC Workshop, Rudel and Lehmann-Horn (1997) stated that the sodium channelopathies can be divided into 3 different forms: paramyotonia, potassium-aggravated myotonia, and periodic paralysis. Potassium-aggravated myotonia includes mild myotonia fluctuans, severe myotonia permanens, and acetazolamide-responsive myotonia.
Recombinant chromosome 8 syndrome
MedGen UID:
167070
Concept ID:
C0795822
Disease or Syndrome
Recombinant 8 syndrome is a condition that involves heart and urinary tract abnormalities, moderate to severe intellectual disability, and a distinctive facial appearance. The characteristic facial features include a wide, square face; a thin upper lip; a downturned mouth; a small chin (micrognathia); wide-set eyes (hypertelorism); and low-set or unusually shaped ears. People with recombinant 8 syndrome may have overgrowth of the gums (gingival hyperplasia) and abnormal tooth development. Males with this condition frequently have undescended testes (cryptorchidism). Some affected individuals have recurrent ear infections (otitis media) or hearing loss. Many children with recombinant 8 syndrome do not survive past early childhood, usually due to complications related to their heart abnormalities.
Chromosome 9, monosomy 9p
MedGen UID:
167073
Concept ID:
C0795830
Disease or Syndrome
Partial deletion of the short arm of chromosome 9 with mental retardation, craniofacial anomalies, abnormal dermatoglyphics, short and webbed neck, heart murmurs, square nails, and other defects.
Chromosome 9q deletion syndrome
MedGen UID:
208639
Concept ID:
C0795833
Disease or Syndrome
Kleefstra syndrome is characterized by intellectual disability, childhood hypotonia, and distinctive facial features. The majority of individuals function in the moderate to severe spectrum of intellectual disability although a few individuals have mild delay and total IQ around 70. Although most have severe expressive speech delay with little speech development, general language development is usually at a higher level, making nonverbal communication possible. A complex pattern of other findings can also be observed including heart defects, renal/urologic defects, genital defects in males, severe respiratory infections, epilepsy/febrile seizures, autistic-like features in childhood, and extreme apathy or catatonic-like features after puberty.
11q partial monosomy syndrome
MedGen UID:
162878
Concept ID:
C0795841
Disease or Syndrome
Jacobsen syndrome is a condition caused by a loss of genetic material from chromosome 11. Because this deletion occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 11q terminal deletion disorder. The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals have delayed development, including the development of motor skills (such as sitting, standing, and walking) and speech. Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention deficit-hyperactivity disorder (ADHD). Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small lower jaw. Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance. More than 90 percent of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising. Paris-Trousseau syndrome is a disorder of platelets, which are blood cell fragments that are necessary for blood clotting. Other features of Jacobsen syndrome can include heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus infections, and skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood.
Smith-Magenis syndrome
MedGen UID:
162881
Concept ID:
C0795864
Disease or Syndrome
Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly facial features that progress with age), developmental delay, cognitive impairment, and behavioral abnormalities. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory integration issues are frequently noted. Children and adults typically have inattention, distractibility, hyperactivity, impulsivity, maladaptive behaviors including frequent outbursts/temper tantrums, attention seeking, disobedience, aggression, toileting difficulties, and self-injurious behaviors (SIB) including self-hitting, self-biting, and/or skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or "self-hug" seems to be highly associated with SMS. The finger lick and page flipping ("lick and flip") behavior may be less prevalent than initially reported. An underlying developmental asynchrony, specifically between intellectual functioning and emotional maturity, may also contribute to maladaptive behaviors in people with SMS.
Chromosome 18, tetrasomy 18p
MedGen UID:
167079
Concept ID:
C0795868
Disease or Syndrome
Tetrasomy 18p is a developmental disorder that affects many parts of the body. This condition usually causes feeding difficulties in infancy, delayed development, intellectual disability, changes in muscle tone, distinctive facial features, and other birth defects. However, the signs and symptoms vary among affected individuals. Babies with tetrasomy 18p often have trouble feeding and may vomit frequently, which makes it difficult for them to gain weight. Some affected infants also have breathing problems and jaundice, which is a yellowing of the skin and the whites of the eyes. Changes in muscle tone are commonly seen with tetrasomy 18p. Some affected children have weak muscle tone (hypotonia), while others have increased muscle tone (hypertonia) and stiffness (spasticity). These changes contribute to delayed development of motor skills, including sitting, crawling, and walking. Tetrasomy 18p is associated with a distinctive facial appearance that can include unusually shaped and low-set ears, a small mouth, a flat area between the upper lip and the nose (philtrum), and a thin upper lip. Many affected individuals also have a high, arched roof of the mouth (palate). Additional features of tetrasomy 18p can include seizures, vision problems, recurrent ear infections, mild to moderate hearing loss, constipation and other gastrointestinal problems, abnormal curvature of the spine (scoliosis or kyphosis), and heart defects. Males with tetrasomy 18p may be born with undescended testes (cryptorchidism) or the opening of the urethra on the underside of the penis (hypospadias). Psychiatric conditions, such as attention deficit hyperactivity disorder (ADHD) and anxiety, have also been reported in some people with tetrasomy 18p.
Allan-Herndon-Dudley syndrome
MedGen UID:
208645
Concept ID:
C0795889
Disease or Syndrome
MCT8-specific thyroid hormone cell-membrane transporter deficiency is characterized by severe cognitive deficiency, infantile hypotonia, diminished muscle mass and generalized muscle weakness, progressive spastic quadriplegia, joint contractures, and dystonic and/or athetoid movement with characteristic paroxysms or kinesigenic dyskinesias. Seizures occur in about 25% of cases. Most affected males never sit or walk independently or lose these abilities over time; most never speak or have severely dysarthric speech. Brain MRI obtained in the first few years of life shows transient delayed myelination, which improves by age four years. Although psychomotor findings observed in affected males do not occur in heterozygous females, the latter often have thyroid test abnormalities intermediate between affected and normal individuals.
Alopecia contractures dwarfism mental retardation
MedGen UID:
167081
Concept ID:
C0795895
Disease or Syndrome
A syndrome of total absence of hair, extreme growth failure, mental retardation, and multiple craniofacial, skeletal, and other abnormalities.
Hypertrichotic osteochondrodysplasia
MedGen UID:
208647
Concept ID:
C0795905
Disease or Syndrome
Cantú syndrome and the related disorders acromegaloid facial appearance (AFA) and hypertrichosis and acromegaloid facial features (HAFF) are characterized by congenital hypertrichosis; distinctive coarse facial features (including broad nasal bridge, wide mouth with full lips and macroglossia); enlarged heart (increased ventricular mass, enlarged chambers, and normal cardiac function); and skeletal abnormalities (thickening of the calvaria, broad ribs, scoliosis, and flaring of the metaphyses). Other cardiovascular abnormalities may include patent ductus arteriosus (PDA) (in 50%), pericardial effusion (20%), and increased vascular tortuosity. Intellect is typically normal; behavioral problems can include anxiety, mood swings, obsessive-compulsive disorder, and tics.
Charcot-Marie-Tooth disease, X-linked recessive, type 4
MedGen UID:
162891
Concept ID:
C0795910
Disease or Syndrome
Charcot-Marie-Tooth (CMT) hereditary neuropathy refers to a group of disorders characterized by a chronic motor and sensory polyneuropathy. The affected individual typically has distal muscle weakness and atrophy often associated with mild to moderate sensory loss, depressed tendon reflexes, and high-arched feet.
Crome syndrome
MedGen UID:
167082
Concept ID:
C0795914
Disease or Syndrome
Cataracts, retarded growth and mental development, epilepsy, and variable neurological and other defects.
Craniofacial malformations, asymmetric, with polysyndactyly and abnormal skin and gut development
MedGen UID:
167083
Concept ID:
C0795915
Disease or Syndrome
A syndrome of unilateral coronal synostosis, plagiocephaly, craniofacial asymmetry, unilateral microphthalmia, iris coloboma, broad thumbs, syndactyly of the hands, polydactyly of the feet, erosive skin lesions, gastrointestinal abnormalities, and moderate developmental delay.
Chromosome 16-related alpha-thalassemia/mental retardation syndrome
MedGen UID:
162892
Concept ID:
C0795917
Disease or Syndrome
Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome is characterized by distinctive craniofacial features, genital anomalies, severe developmental delays, hypotonia, intellectual disability, and mild-to-moderate anemia secondary to alpha-thalassemia. Craniofacial abnormalities include small head circumference, telecanthus or widely spaced eyes, short nose, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip with coarsening of the facial features over time. Although all affected individuals have a normal 46,XY karyotype, genital anomalies range from hypospadias and undescended testicles to severe hypospadias and ambiguous genitalia, to normal-appearing female external genitalia. Global developmental delays are evident in infancy and some affected individuals never walk independently or develop significant speech.
Edinburgh malformation syndrome
MedGen UID:
167084
Concept ID:
C0795933
Disease or Syndrome
A syndrome reported in an Edinburgh family in which five infants (four female and one male) were found to have a characteristic facial appearance, hydrocephalus, and psychomotor retardation. Some characteristics of this syndrome are similar to those of the de Lange syndrome 1.
Faciocardiorenal syndrome
MedGen UID:
208649
Concept ID:
C0795936
Disease or Syndrome
A syndrome of characteristic facies, horseshoe kidney, congenital heart defect, and delayed mental and physical development.
Filippi syndrome
MedGen UID:
163197
Concept ID:
C0795940
Disease or Syndrome
Filippi syndrome is characterized by short stature, microcephaly, syndactyly, intellectual disability, and facial dysmorphism consisting of bulging forehead, broad and prominent nasal bridge, and diminished alar flare. Common features include cryptorchidism, speech impairment, and clinodactyly of the fifth finger, Some patients exhibit visual disturbances, polydactyly, seizures, and/or ectodermal abnormalities, such as nail hypoplasia, long eyelashes, hirsutism, and microdontia (summary by Hussain et al., 2014).
Fine-Lubinsky syndrome
MedGen UID:
163198
Concept ID:
C0795941
Disease or Syndrome
A dysmorphic syndrome with variable expression characterized mainly by body asymmetry, developmental delay, brachycephaly, cataracts, and deafness.
Fitzsimmons-Guilbert syndrome
MedGen UID:
163199
Concept ID:
C0795942
Disease or Syndrome
Fountain syndrome
MedGen UID:
208650
Concept ID:
C0795944
Disease or Syndrome
Coarse facies, mental retardation, hearing loss, and skeletal abnormalities are the major symptoms.
Subaortic stenosis short stature syndrome
MedGen UID:
167085
Concept ID:
C0795947
Disease or Syndrome
Mental and somatic retardation with Peters anomaly (defect of the Descemet membrane and deep stromal layers of the cornea), corneal clouding, hypoplastic facies, subvalvular aortic stenosis, and skeletal abnormalities.
Microcephaly, hiatal hernia and nephrotic syndrome
MedGen UID:
167086
Concept ID:
C0795949
Disease or Syndrome
Galloway-Mowat syndrome is a rare autosomal recessive disorder characterized by microcephaly and central nervous system abnormalities resulting in severe intellectual disability. Most patients also develop seizures and nephrotic syndrome later in childhood. Many affected children die in the first decade of life (summary by Colin et al., 2014).
Andermann syndrome
MedGen UID:
162893
Concept ID:
C0795950
Disease or Syndrome
Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and neurodegenerative disorder, is characterized by severe progressive sensorimotor neuropathy with resulting hypotonia, areflexia, and amyotrophy and variable degrees of dysgenesis of the corpus callosum. Mild-to-severe intellectual disability and "psychotic episodes" during adolescence are observed. Sensory modalities are moderately to severely affected beginning in infancy. The average age of onset of walking is 3.8 years; the average age of loss of walking is 13.8 years; the average age of death is 33 years.
Spastic paraplegia 1
MedGen UID:
162894
Concept ID:
C0795953
Disease or Syndrome
The phenotypic spectrum of L1 syndrome includes: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS); MASA syndrome (mental retardation, aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs); SPG1 (X-linked complicated hereditary spastic paraplegia type 1); and X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50).
Gomez Lopez Hernandez syndrome
MedGen UID:
163201
Concept ID:
C0795959
Disease or Syndrome
Cerebellotrigeminal dermal dysplasia, also known as Gomez-Lopez-Hernandez (GLH) syndrome, is a rare neurocutaneous syndrome classically characterized by the triad of rhombencephalosynapsis, trigeminal anesthesia, often giving rise to corneal opacities, and bilateral parietal or parietooccipital alopecia, However, trigeminal anesthesia is an inconsistent finding (summary by Sukhudyan et al., 2010).
Mental retardation Gustavson type, X-linked
MedGen UID:
167088
Concept ID:
C0795965
Disease or Syndrome
Mental retardation syndrome with microcephaly, severely impaired vision, hearing defect, epileptic seizures, restricted movement, and early death.
Harrod Doman Keele syndrome
MedGen UID:
162895
Concept ID:
C0795970
Disease or Syndrome
A rare syndrome of microcephaly with a long thin face and pointed chin, small mouth, malformed ears, hypotelorism, arachnodactyly, hypogenitalism and mental retardation.
Bullous dystrophy hereditary macular type
MedGen UID:
167089
Concept ID:
C0795974
Disease or Syndrome
A skin disease characterized by formation of bullae without evidence of trauma, hyperpigmentation or hypopigmentation and acrocyanosis in association with microcephaly, subnormal growth and mental development, short tapering fingers, and occasionally deformed nails.
Wiedemann Oldigs Oppermann syndrome
MedGen UID:
163202
Concept ID:
C0795976
Disease or Syndrome
A combination of congenital anomalies consisting of hirsutism, brachycephaly, abnormal position of thumbs, pedes excavatio with claw-toes, facial abnormalities, and mental deficiency.
Hypospadias mental retardation Goldblatt type
MedGen UID:
162896
Concept ID:
C0795989
Disease or Syndrome
Hypospadias, retarded mental development, microcephaly, craniofacial dysmorphism, joint laxity, and beaked nails.
Johnson neuroectodermal syndrome
MedGen UID:
167092
Concept ID:
C0796002
Disease or Syndrome
A syndrome with variable expressivity characterized by alopecia with mild facial asymmetry and micrognathia which give the face its characteristic features, ear abnormalities with hearing loss, loss of the sense of smell, hypogonadism, dental caries, and occasional mental deficiency.
Mental retardation-hypotonic facies syndrome X-linked, 1
MedGen UID:
167093
Concept ID:
C0796003
Disease or Syndrome
The term 'X-linked mental retardation-hypotonic facies syndrome' comprises several syndromes previously reported separately. These include Juberg-Marsidi, Carpenter-Waziri, Holmes-Gang, and Smith-Fineman-Myers syndromes as well as 1 family with X-linked mental retardation with spastic paraplegia. All these syndromes were found to be caused by mutation in the XH2 gene and are characterized primarily by severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women (Abidi et al., 2005). Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects. X-linked alpha-thalassemia/mental retardation syndrome (ATR-X; 301040) is an allelic disorder with a similar phenotype with the addition of alpha-thalassemia and Hb H inclusion bodies in erythrocytes.
Kapur Toriello syndrome
MedGen UID:
208654
Concept ID:
C0796005
Disease or Syndrome
Retarded mental and growth development with variable congenial defects, including heart abnormalities, intestinal malrotation, characteristic facies, and other anomalies.
Peters plus syndrome
MedGen UID:
163204
Concept ID:
C0796012
Disease or Syndrome
Peters plus syndrome is characterized by anterior chamber eye anomalies, short limbs with broad distal extremities, variable developmental delay/intellectual disability, characteristic facial features, and cleft lip/palate. The most common anterior chamber defect is Peters' anomaly, consisting of central corneal clouding, thinning of the posterior cornea, and iridocorneal adhesions. Cataracts and glaucoma are common. Developmental delay is observed in about 80% of children; while some adults have normal cognitive function, intellectual disability can range from mild to severe. Cleft lip is present in 45% and cleft palate in 33%.
Laband syndrome
MedGen UID:
208656
Concept ID:
C0796013
Disease or Syndrome
Zimmermann-Laband syndrome is a rare disorder characterized by gingival fibromatosis, dysplastic or absent nails, hypoplasia of the distal phalanges, scoliosis, hepatosplenomegaly, hirsutism, and abnormalities of the cartilage of the nose and/or ears (summary by Balasubramanian and Parker, 2010).
Spastic paraplegia 23
MedGen UID:
167094
Concept ID:
C0796019
Disease or Syndrome
Progressive spastic paresis, widespread skin pigmentation changes, characteristic facies, and mental retardation in some cases.
Lowry Maclean syndrome
MedGen UID:
167095
Concept ID:
C0796020
Disease or Syndrome
Mental deficiency with multiple abnormalities consisting of ocular proptosis, glaucoma, cleft palate, diaphragmatic eventration, cardiovascular defects, growth failure, and craniosynostosis. The originally-reported case was sporadic.
Lowry Wood syndrome
MedGen UID:
162899
Concept ID:
C0796021
Disease or Syndrome
A syndrome multiple epiphyseal dysplasia (MED) microcephaly, and nystagmus with retinitis pigmentosa, and mental retardation in some cases.
Mac Dermot Winter syndrome
MedGen UID:
162900
Concept ID:
C0796024
Disease or Syndrome
A syndrome of prenatal growth deficiency, microcephaly, dysmorphic facies, absent psychomotor development, hypoplastic genitalia, convulsions, and other disorders.
Arts syndrome
MedGen UID:
163205
Concept ID:
C0796028
Disease or Syndrome
Arts syndrome, which is part of the spectrum of PRPS1-related disorders, is characterized by profound congenital sensorineural hearing impairment, early-onset hypotonia, delayed motor development, mild to moderate intellectual disability, ataxia, and increased risk of infection, all of which (with the exception of optic atrophy) present before age two years. Signs of peripheral neuropathy develop during early childhood. Twelve of 15 boys from the two Dutch families reported with Arts syndrome died before age six years of complications of infection. Carrier females can show late-onset (age >20 years) hearing impairment and other findings.
Marden-Walker syndrome
MedGen UID:
163206
Concept ID:
C0796033
Disease or Syndrome
A constellation of immobile facies, blepharophimosis, micrognathia, microcephaly, midfacial hypoplasia, multiple contractures, hypotonia, arachnodactyly, developmental delay, and other anomalies.
Martsolf syndrome
MedGen UID:
208658
Concept ID:
C0796037
Disease or Syndrome
Mental deficiency, gonadal hypofunction, short stature, "old looking" face, cataracts, and other defects.
McDonough syndrome
MedGen UID:
162902
Concept ID:
C0796038
Disease or Syndrome
A syndrome of psychomotor retardation, characteristic facies, kyphoscoliosis, diastasis recti, cryptorchidism, and congenital heart defect. Named after Dr. Kenneth B. McDonough, who referred to the authors the original family affected with this syndrome
Reardon Wilson Cavanagh syndrome
MedGen UID:
208659
Concept ID:
C0796045
Disease or Syndrome
Ataxia, deafness, mental retardation, and upper and lower neuron disease are the principal symptoms.
Gurrieri syndrome
MedGen UID:
208660
Concept ID:
C0796046
Disease or Syndrome
A syndrome of short stature with retarded bone age, cerebral atrophy, epilepsy, ocular anomalies, skeletal defects, and moderate to severe mental deficiency.
Mercaptolactate-cysteine disulfiduria
MedGen UID:
208661
Concept ID:
C0796055
Disease or Syndrome
Mercaptolactate-cysteine disulfiduria with mental retardation, seizures, flat nasal bridge, and highly arched palate.
Microcephaly deafness syndrome
MedGen UID:
163208
Concept ID:
C0796062
Disease or Syndrome
A syndrome of microcephaly, dysmorphic facies, deafness, and mental retardation.
Microcephaly cervical spine fusion anomalies
MedGen UID:
208663
Concept ID:
C0796066
Disease or Syndrome
Microcephaly, retarded mental and growth development, characteristic facies, and cervical spine fusion.
Dwarfism, mental retardation and eye abnormality
MedGen UID:
208664
Concept ID:
C0796076
Disease or Syndrome
Delayed growth and mental development with ocular disorders.
Intellectual deficit Buenos-Aires type
MedGen UID:
167102
Concept ID:
C0796080
Disease or Syndrome
A syndrome of mental and physical retardation, cardiac and renal malformations, and peculiar facies.
Myhre syndrome
MedGen UID:
167103
Concept ID:
C0796081
Disease or Syndrome
Myhre syndrome is a rare disorder characterized by mental retardation, dysmorphic facial features, including microcephaly, midface hypoplasia, prognathism, and blepharophimosis, as well as typical skeletal anomalies, including short stature, square body shape, broad ribs, iliac hypoplasia, brachydactyly, flattened vertebrae, and thickened calvaria. Other features, such as congenital heart disease, may also occur. All reported cases have been sporadic (summary by Bachmann-Gagescu et al., 2011).
Nance-Horan syndrome
MedGen UID:
208665
Concept ID:
C0796085
Disease or Syndrome
Nance-Horan syndrome is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation (summary by Burdon et al., 2003).
Megalocornea mental retardation syndrome
MedGen UID:
162904
Concept ID:
C0796086
Disease or Syndrome
Megalocornea and iris anomalies accompanied by facial and skeletal defects, slow psychomotor development, hypotonia, and seizures. Later reports classify megalocornea-mental retardation syndrome into several types: Type 1 Synonym: Neuhauser syndrome With iris hypoplasia and minor abnormalities. Type 2 With camptodactyly, scoliosis, and growth retardation. Type 3 Synonym: Verloes type With macrocephaly, hypotonia, and other minor anomalies but no hypoplasia of the irides. Type 4 With megalocephaly,obesity, and normal irides.
Neurofaciodigitorenal syndrome
MedGen UID:
163212
Concept ID:
C0796088
Disease or Syndrome
A syndrome of multiple craniofacial anomalies (prominent forehead, ear anomalies, vertical groove on the tip of the nose, megalocephaly, and cowlick), possible heart defect, finger and foot abnormalities, abnormal EEG, developmental delay, and kidney agenesis originally reported in one of two brothers..
Oculocerebrocutaneous syndrome
MedGen UID:
163214
Concept ID:
C0796092
Disease or Syndrome
Orbital cysts and other eye defects, multiple cerebral anomalies, and focal dermal defects are the principal characteristics of this syndrome.
Mental retardation, congenital heart disease, blepharophimosis, blepharoptosis and hypoplastic teeth
MedGen UID:
162905
Concept ID:
C0796094
Disease or Syndrome
A syndrome of delayed development, blepharophimosis, blepharoptosis, dental hypoplasia, deafness, heart defect, cryptorchidism and scrotal hypoplasia in males, and other abnormalities.
C syndrome
MedGen UID:
167105
Concept ID:
C0796095
Disease or Syndrome
The C syndrome, also known as Opitz trigonocephaly syndrome, is a malformation syndrome characterized by trigonocephaly, severe mental retardation, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears (summary by Kaname et al., 2007). C syndrome shows phenotypic overlap with Bohring-Opitz syndrome, or C-like syndrome (605039), a disorder with more severe features than C syndrome, caused by heterozygous mutation in the ASXL1 gene (612990) on chromosome 20q11.
Cleft lip/palate with abnormal thumbs and microcephaly
MedGen UID:
162906
Concept ID:
C0796099
Disease or Syndrome
Orofaciodigital syndrome 8
MedGen UID:
208667
Concept ID:
C0796101
Disease or Syndrome
Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes). Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder. The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability. Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums. Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism). Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome. Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.
Pallister W syndrome
MedGen UID:
163215
Concept ID:
C0796110
Disease or Syndrome
Mental retardation with characteristic pugilistic facies (flat nose, frontal prominence, hypertelorism, downslanting palpebral fissures, and anterior cowlick), midline notch on the upper lip, cleft palate, spasticity, and various musculoskeletal anomalies. The original cases were reported in brothers R. W. and S. W., hence the synonym W syndrome.
Renal hamartomas nephroblastomatosis and fetal gigantism
MedGen UID:
162909
Concept ID:
C0796113
Disease or Syndrome
Perlman syndrome is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor, with a 64% incidence in infants surviving beyond the neonatal period. The tumor is diagnosed at an earlier age in these individuals compared with sporadic cases (less than 2 years and 3-4 years of age, respectively), and there is a high frequency of bilateral tumors (55%). Histologic examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor (summary by Astuti et al., 2012).
Primrose syndrome
MedGen UID:
162911
Concept ID:
C0796121
Disease or Syndrome
Primrose syndrome consists of recognizable facial features, macrocephaly, mental retardation, enlarged and calcified external ears, sparse body hair, and distal muscle wasting (summary by Carvalho and Speck-Martins, 2011). Patients with a deletion syndrome involving 3q13.31 (615433) exhibit features overlapping those of Primrose syndrome.
Cataract ataxia deafness
MedGen UID:
163216
Concept ID:
C0796123
Disease or Syndrome
Mild mental deficiency with cataracts, ataxia, deafness, polyneuropthy, and other disorders.
Proud Levine Carpenter syndrome
MedGen UID:
163217
Concept ID:
C0796124
Disease or Syndrome
Proud syndrome is an X-linked developmental disorder characterized by agenesis of the corpus callosum, severe mental retardation, seizures, and spasticity. Males are severely affected, whereas females may be unaffected or have a milder phenotype (Proud et al., 1992). Proud syndrome is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome to infantile spasms without brain malformations (EIEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008).
Pseudoprogeria syndrome
MedGen UID:
163218
Concept ID:
C0796125
Disease or Syndrome
A Hallermann-Streiff-like syndrome marked by presenile facies suggesting progeria, absent eyebrows and eyelashes, beaked nose, eye abnormalities, spinal defects, osteoporosis, and other disorders.
Ramon Syndrome
MedGen UID:
208669
Concept ID:
C0796133
Disease or Syndrome
A slowly progressive syndrome of cherubic facies (fullness of the cheeks, producing a typical chubby face suggestive of a cherub) maxillary fibrous dysplasia, gingival enlargement, radiolucent lesions of the jaws, seizures, delayed mental development, stunted growth, and other defects. Insulin dependent diabetes mellitus and vascular skin lesions may occur.
Renpenning syndrome 1
MedGen UID:
208670
Concept ID:
C0796135
Disease or Syndrome
Renpenning syndrome is an X-linked mental retardation syndrome with clinically recognizable features. Affected individuals have microcephaly, short stature, small testes, and dysmorphic facies, including tall narrow face, upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies. Stevenson et al. (2005) proposed that the various X-linked mental retardation syndromes due to PQBP1 mutations be combined under the name of Renpenning syndrome.
Richards-Rundle syndrome
MedGen UID:
163219
Concept ID:
C0796136
Disease or Syndrome
Hearing loss, mental retardation, ataxia, hypogonadism, peripheral muscle wasting, and ketoaciduria progressing from childhood and eventually becoming static.
Dandy-Walker like malformation with atrioventricular septal defect
MedGen UID:
163220
Concept ID:
C0796137
Disease or Syndrome
The 3C syndrome, also known as Ritscher-Schinzel syndrome, is a developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay (summary by Leonardi et al., 2001; Seidahmed et al., 2011).
Rutherfurd syndrome
MedGen UID:
163222
Concept ID:
C0796140
Disease or Syndrome
A mild form of gingival hypertrophy with corneal opacity and failure of tooth eruption. Mental retardation and aggressive behavior have been noted but it is not certain whether they are related to this syndrome.
Sao paulo mca/mr syndrome
MedGen UID:
162914
Concept ID:
C0796142
Disease or Syndrome
The Richieri-Costa/Guion-Almeida syndrome is characterized by mild mental retardation, short stature, microbrachycephaly, ptosis, esotropia, cleft lip/palate.
Acrocallosal syndrome, Schinzel type
MedGen UID:
162915
Concept ID:
C0796147
Disease or Syndrome
Classic Joubert syndrome is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS) . Hypotonia. Developmental delays . Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. The designation Joubert syndrome and related disorders (JSRD) is used to describe individuals with JS who have additional findings including retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Simpson-Golabi-Behmel syndrome
MedGen UID:
162917
Concept ID:
C0796154
Disease or Syndrome
Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is characterized by pre- and postnatal macrosomia; distinctive craniofacies (including macrocephaly, coarse facial features, macrostomia, macroglossia, palatal abnormalities); and commonly, mild to severe intellectual disability with or without structural brain anomalies. Other variable findings include supernumerary nipples, diastasis recti/umbilical hernia, congenital heart defects, diaphragmatic hernia, genitourinary defects, and GI anomalies. Skeletal anomalies can include vertebral fusion, scoliosis, rib anomalies, and congenital hip dislocation. Hand anomalies can include large hands and postaxial polydactyly. Affected individuals are at increased risk for embryonal tumors, including Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, and hepatocellular carcinoma.
Prader-Willi habitus, osteopenia, and camptodactyly
MedGen UID:
162919
Concept ID:
C0796189
Disease or Syndrome
A triad of genital anomalies, mental retardation, and obesity associated with contractures of the hands and generalized osteoporosis.
Van Den Bosch syndrome
MedGen UID:
162920
Concept ID:
C0796192
Disease or Syndrome
Mental deficiency, choroideremia, acrokeratosis verruciformis, anhidrosis, and bone abnormalities.
Parkinsonism, early onset with mental retardation
MedGen UID:
208674
Concept ID:
C0796195
Disease or Syndrome
Waisman syndrome is an X-linked recessive neurologic disorder characterized by delayed psychomotor development, intellectual disability, and early-onset Parkinson disease (summary by Wilson et al., 2014).
Pashayan syndrome
MedGen UID:
163226
Concept ID:
C0796197
Disease or Syndrome
Telecanthus, displacement of the lacrimal puncta, lacrimal defects, masklike facies, and mental deficiency.
Wieacker syndrome
MedGen UID:
163227
Concept ID:
C0796200
Disease or Syndrome
Wieacker-Wolff syndrome is a severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show mental retardation. Carrier females may have mild features of the disorder (summary by Hirata et al., 2013).
Wittwer syndrome
MedGen UID:
162921
Concept ID:
C0796202
Disease or Syndrome
Mental retardation with multiple congenital abnormalities consisting of craniofacial anomalies, delayed development, skeletal anomalies, urogenital anomalies, and deformed hands.
Woods syndrome
MedGen UID:
490089
Concept ID:
C0796203
Disease or Syndrome
A craniodigital syndrome of prenatal growth retardation, microcephaly, mental retardation, syndactyly of the fingers, and minor facial anomalies.
Worster Drought syndrome
MedGen UID:
163228
Concept ID:
C0796204
Disease or Syndrome
A syndrome with variable expression characterized by suprabulbar paresis, selective weakness and impairment of movement of the orbicularis oris muscle, tongue, and soft palate, resulting in speech and swallowing difficulty.
Atkin syndrome
MedGen UID:
163230
Concept ID:
C0796206
Disease or Syndrome
C-like syndrome
MedGen UID:
208678
Concept ID:
C0796232
Disease or Syndrome
Bohring-Opitz syndrome is a malformation syndrome characterized by severe intrauterine growth retardation, poor feeding, profound mental retardation, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints (summary by Hoischen et al., 2011). See also the C syndrome (211750), a disorder with a similar phenotype caused by heterozygous mutation in the CD96 gene (606037) on chromosome 3q13.
Acrofacial dysostosis, catania type
MedGen UID:
163236
Concept ID:
C0796243
Disease or Syndrome
Mental retardation X-linked syndromic 5
MedGen UID:
162924
Concept ID:
C0796254
Disease or Syndrome
Pettigrew syndrome is characterized by mental retardation and highly variable additional features, including choreoathetosis, hydrocephalus, Dandy-Walker malformation, seizures, and iron or calcium deposition in the brain, both between and within families (summary by Cacciagli et al., 2014). See 311510 for another X-linked mental retardation syndrome associated with basal ganglia disease (Waisman syndrome). See 220219 for another mental retardation syndrome with Dandy-Walker malformation.
Monoamine oxidase A deficiency
MedGen UID:
208683
Concept ID:
C0796275
Disease or Syndrome
Brunner syndrome is a recessive X-linked disorder characterized by impulsive aggressiveness and mild mental retardation associated with MAOA deficiency (Brunner et al., 1993).
Acromegaloid facial appearance syndrome
MedGen UID:
167116
Concept ID:
C0796280
Disease or Syndrome
Coarse (acromegaloid) facies with thick lips, overgrowth of the intraoral mucosa, blepharophimosis, and bulbous nose in association with dull mentality and other disorders.
CAHMR syndrome
MedGen UID:
167117
Concept ID:
C0796282
Disease or Syndrome
A syndrome consisting mainly of cataracts, hypertrichosis, and mental retardation.
Danon disease
MedGen UID:
209235
Concept ID:
C0878677
Disease or Syndrome
Danon disease is an X-linked dominant disorder predominantly affecting cardiac muscle. Skeletal muscle involvement and mental retardation are variable features. The accumulation of glycogen in muscle and lysosomes originally led to the classification of Danon disease as a variant of glycogen storage disease II (Pompe disease; 232300) with 'normal acid maltase' or alpha-glucosidase (GAA; 606800) (Danon et al., 1981). However, Nishino et al. (2000) stated that Danon disease is not a glycogen storage disease because glycogen is not always increased. Sugie et al. (2005) classified Danon disease as a form of autophagic vacuolar myopathy, characterized by intracytoplasmic autophagic vacuoles with sarcolemmal features. The characteristic vacuole is believed to be an autolysosome surrounded by secondarily-generated membranes containing sarcolemmal proteins, basal lamina, and acetylcholinesterase activity. X-linked myopathy with excessive autophagy (XMEA; 310440) is a distinct disorder with similar pathologic features.
McKusick Kaufman syndrome
MedGen UID:
184924
Concept ID:
C0948368
Congenital Abnormality
McKusick-Kaufman syndrome (MKS) is characterized by the combination of postaxial polydactyly (PAP), congenital heart disease (CHD), and hydrometrocolpos (HMC) in females and genital malformations in males (most commonly hypospadias, cryptorchidism, and chordee). HMC in infants usually presents as a large cystic abdominal mass arising out of the pelvis, caused by dilatation of the vagina and uterus as a result of the accumulation of cervical secretions from maternal estrogen stimulation. HMC can be caused by failure of the distal third of the vagina to develop (vaginal agenesis), a transverse vaginal membrane, or an imperforate hymen. Cardiac malformations that have been described at least once in individuals with MKS include atrioventricularis (AV) communis with a left-sided superior vena cava, atrial septal defect, ventricular septal defect, AV canal, small aorta and hypoplastic left ventricle, tetralogy of Fallot, and patent ductus arteriosus.
Nicolaides-Baraitser syndrome
MedGen UID:
220983
Concept ID:
C1303073
Disease or Syndrome
Nicolaides-Baraitser syndrome (NCBRS) is characterized by severe mental retardation, early-onset seizures, short stature, dysmorphic facial features, and sparse hair (summary by Sousa et al., 2009).
Shprintzen-Goldberg syndrome
MedGen UID:
231160
Concept ID:
C1321551
Congenital Abnormality
Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males, are also characteristic findings.
Oral-facial-digital syndrome
MedGen UID:
307142
Concept ID:
C1510460
Disease or Syndrome
Oral-facial-digital syndrome type I (OFD1) is associated with dysfunction of primary cilia and is characterized by the following abnormalities: Oral (lobed tongue, hamartomas or lipomas of the tongue, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities). Facial (widely spaced eyes or telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft upper lip, micrognathia) . Digital (brachydactyly, syndactyly of varying degrees, and clinodactyly of the fifth finger; duplicated hallux [great toe]; preaxial or postaxial polydactyly of the hands). Brain (intracerebral cysts, corpus callosum agenesis, cerebellar agenesis with or without Dandy-Walker malformation) . Kidney (polycystic kidney disease). As many as 50% of individuals with OFD1 have some degree of intellectual disability, which is usually mild. Almost all affected individuals are female. However, males with OFD1 have been described, mostly as malformed fetuses delivered by women with OFD1.
Jung Wolff Back Stahl syndrome
MedGen UID:
316973
Concept ID:
C1832362
Disease or Syndrome
Cold-induced sweating syndrome
MedGen UID:
321950
Concept ID:
C1832409
Disease or Syndrome
Crisponi syndrome, the infantile presentation of cold-induced sweating syndrome (CISS), is characterized by dysmorphic features (distinctive facies; lower facial weakness; flexion deformity at the elbows; camptodactyly with fisted hands; misshapen feet and overriding toes); poor suck reflex and severely impaired swallowing; and often temperature spikes with increased risk of seizures and sudden death. During the first decade of life, children with CISS develop profuse sweating of their face, arms, and chest with ambient temperatures below 18º to 22º C and often with other stimuli including apprehension or ingestion of sweets. Affected individuals sweat very little in hot environments and may feel overheated. In the second decade, progressive thoracolumbar kyphoscoliosis requires intervention.
Genoa syndrome
MedGen UID:
330464
Concept ID:
C1832424
Disease or Syndrome
Holoprosencephaly (HPE) is a structural anomaly of the brain in which there is failed or incomplete separation of the forebrain early in gestation. Classic HPE encompasses a continuum of brain malformations including (in order of decreasing severity): alobar, semilobar, lobar, and middle interhemispheric variant (MIHV) type HPE; a septopreoptic type has also been described. Other CNS abnormalities not specific to HPE may also occur. HPE is accompanied by a spectrum of characteristic craniofacial anomalies in approximately 80% of individuals with HPE. Developmental delay is present in virtually all individuals with the HPE spectrum of CNS anomalies. Seizures and pituitary dysfunction are common. Most affected fetuses do not survive; severely affected children typically do not survive beyond early infancy, while a significant proportion of more mildly affected children survive past 12 months. Mildly manifesting individuals without appreciable brain anomalies on conventional neuroimaging may be described as having “microform” HPE.
DiGeorge syndrome/velocardiofacial syndrome complex 2
MedGen UID:
321954
Concept ID:
C1832431
Disease or Syndrome
Microcephaly, congenital heart disease, unilateral renal agenesis, and hyposegmented lungs
MedGen UID:
371329
Concept ID:
C1832436
Disease or Syndrome
Mental retardation, microcephaly, epilepsy, and coarse face
MedGen UID:
330468
Concept ID:
C1832437
Disease or Syndrome
Chitty Hall Baraitser syndrome
MedGen UID:
371330
Concept ID:
C1832438
Disease or Syndrome
Microphthalmia syndromic 8
MedGen UID:
330469
Concept ID:
C1832440
Disease or Syndrome
Potocki-Shaffer syndrome
MedGen UID:
318657
Concept ID:
C1832588
Disease or Syndrome
Potocki-Shaffer syndrome is a rare contiguous gene deletion syndrome due to haploinsufficiency of the 11p12-p11.2 region and is characterized by craniofacial abnormalities, developmental delay, intellectual disability, multiple exostoses (168500), and biparietal foramina (605957) (summary by Swarr et al., 2010).
Alopecia-mental retardation syndrome with convulsions and hypergonadotropic hypogonadism
MedGen UID:
321990
Concept ID:
C1832593
Disease or Syndrome
Fallot complex with severe mental and growth retardation
MedGen UID:
322025
Concept ID:
C1832735
Disease or Syndrome
Congenital disorder of glycosylation type 1D
MedGen UID:
322026
Concept ID:
C1832736
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Choreoathetosis/spasticity, episodic
MedGen UID:
371427
Concept ID:
C1832855
Disease or Syndrome
Dystonia-9 is an autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most show some degree of cognitive impairment. Other variable features may include seizures, migraine headaches, and ataxia (summary by Weber et al., 2011).
Hydrocephalus, skeletal anomalies, and mental disturbance
MedGen UID:
318750
Concept ID:
C1832948
Disease or Syndrome
Craniosynostosis 4
MedGen UID:
322167
Concept ID:
C1833340
Disease or Syndrome
Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (Fitzpatrick, 2013). Mutation in the ERF gene has been found to cause several forms of craniosynostosis, including lambdoid, sagittal, metopic, coronal, and multisuture. For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
Hypertryptophanemia, familial
MedGen UID:
322223
Concept ID:
C1833562
Disease or Syndrome
Ophthalmoplegia, progressive, with scrotal tongue and mental deficiency
MedGen UID:
318972
Concept ID:
C1833835
Disease or Syndrome
Blepharofacioskeletal syndrome
MedGen UID:
371716
Concept ID:
C1834038
Disease or Syndrome
Schilbach-Rott syndrome is an autosomal dominant disorder characterized by hypotelorism, epicanthal folds, cleft palate, dysmorphic facies, and hypospadias in males. The phenotype is variable; mild mental retardation has been reported (summary by Shkalim et al., 2009).
Jankovic Rivera syndrome
MedGen UID:
371854
Concept ID:
C1834569
Disease or Syndrome
Spinal muscular atrophy with progressive myoclonic epilepsy is an autosomal recessive neuromuscular disorder characterized by childhood onset of proximal muscle weakness and generalized muscular atrophy due to degeneration of spinal motor neurons, followed by the onset of myoclonic seizures. The disorder is progressive, and usually results in loss of ambulation and early death from respiratory insufficiency (summary by Zhou et al., 2012).
MOMO syndrome
MedGen UID:
371897
Concept ID:
C1834759
Disease or Syndrome
Macules hereditary congenital hypopigmented and hyperpigmented
MedGen UID:
371988
Concept ID:
C1835172
Disease or Syndrome
Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation
MedGen UID:
320559
Concept ID:
C1835265
Disease or Syndrome
Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation is an autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes (summary by Ostergaard et al., 2012). Robitaille et al. (2014) found that MCLMR includes a broader spectrum of ocular disease, including retinal detachment with avascularity of the peripheral retina, and noted phenotypic overlap with familial exudative vitreoretinopathy (FEVR; see EVR1, 133780). An autosomal recessive form of microcephaly with chorioretinopathy (251270) is caused by mutation in the TUBGCP6 gene (610053) on chromosome 22q. See also Mirhosseini-Holmes-Walton syndrome (autosomal recessive microcephaly with pigmentary retinopathy and mental retardation; 268050), which has been mapped to chromosome 8q21.3-q22.1. A patient with microcephaly, congenital retinal fold, mental retardation, and lymphedema who had a pericentric inversion of chromosome 6 resulting in haploinsufficiency of the CDK19 gene (614720) has been reported.
Larsen syndrome, dominant type
MedGen UID:
320634
Concept ID:
C1835564
Disease or Syndrome
The FLNB-related disorders include a spectrum of phenotypes ranging from mild (spondylocarpotarsal synostosis [SCT] syndrome and Larsen syndrome) to severe (atelosteogenesis types I [AOI] and III [AOIII], boomerang dysplasia). SCT syndrome is characterized by disproportionate short stature, block vertebrae, scoliosis and lordosis, carpal and tarsal fusion, club feet, hearing loss, dental enamel hypoplasia, and mild facial dysmorphisms. Larsen syndrome is characterized by congenital dislocations of the hip, knee, and elbow; club feet (equinovarus or equinovalgus foot deformities); scoliosis and cervical kyphosis, which can be associated with a cervical myelopathy; short, broad, spatulate distal phalanges; and distinctive craniofacies (prominent forehead, depressed nasal bridge, malar flattening, andwidely spaced eyes). Both can have midline cleft palate and conductive hearing loss. AOIII and AOI are characterized by severe short-limbed dwarfism; dislocated hips, knees, and elbows; and club feet. AOI is lethal in the perinatal period.
Congenital disorder of glycosylation type 1M
MedGen UID:
332072
Concept ID:
C1835849
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome
MedGen UID:
332113
Concept ID:
C1836033
Disease or Syndrome
CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome refers to a unique constellation of clinical manifestations including microcephaly, severe neurologic impairment, psychomotor retardation, failure to thrive, and facial dysmorphism, as well as palmoplantar keratoderma and late-onset ichthyosis. Brain magnetic resonance imaging (MRI) shows various degrees of cerebral dysgenesis including absence of corpus callosum and cortical dysplasia. The syndrome has been found to be uniformly fatal between the ages of 5 and 12 years (Fuchs-Telem et al., 2011).
Goldberg-Shprintzen megacolon syndrome
MedGen UID:
332131
Concept ID:
C1836123
Disease or Syndrome
Goldberg-Shprintzen syndrome is an autosomal recessive multiple congenital anomaly syndrome characterized by intellectual disability, microcephaly, and dysmorphic facial features. Most patients also have Hirschsprung disease and/or gyral abnormalities of the brain, consistent with defects in migration of neural crest cells and neurons. Other features, such as megalocornea or urogenital anomalies, may also be present. Goldberg-Shprintzen syndrome has some resemblance to Mowat-Wilson syndrome (MOWS; 235730) but is genetically distinct (summary by Drevillon et al., 2013). Yomo et al. (1991) referred to this disorder as Goldberg-Shprintzen syndrome, which should not be confused with Shprintzen-Goldberg craniosynostosis syndrome (182212) or 2 other Shprintzen syndromes (192430, 182210).
Cerebrorenodigital syndrome with limb malformations and triradiate acetabula
MedGen UID:
373053
Concept ID:
C1836287
Disease or Syndrome
Kanzaki disease
MedGen UID:
324539
Concept ID:
C1836522
Disease or Syndrome
Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder with atypical features. It is clinically heterogeneous with 3 main phenotypes: type I is an infantile-onset neuroaxonal dystrophy (609241); type II, also known as Kanzaki disease, is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment; and type III is an intermediate disorder (see 609241) with mild to moderate neurologic manifestations (Desnick and Schindler, 2001).
Schindler disease, type 1
MedGen UID:
373113
Concept ID:
C1836544
Disease or Syndrome
Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder. It is clinically heterogeneous with 3 main phenotypes: type I is an infantile-onset neuroaxonal dystrophy; type II, also known as Kanzaki disease (609242), is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment; and type III is an intermediate disorder with mild to moderate neurologic manifestations (Desnick and Schindler, 2001).
Congenital disorder of glycosylation type 1F
MedGen UID:
322968
Concept ID:
C1836669
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. Different forms of CDGs can be recognized by altered isoelectric focusing (IEF) patterns of serum transferrin. For a general discussion of CDGs, see CDG Ia (212065) and CDG Ib (602579).
Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease
MedGen UID:
373160
Concept ID:
C1836727
Disease or Syndrome
The neurologic variant of Waardenburg-Shah syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. (2004) proposed the acronym PCWH for this disorder.
Leukodystrophy, hypomyelinating, 2
MedGen UID:
325157
Concept ID:
C1837355
Disease or Syndrome
Congenital disorder of glycosylation type 1E
MedGen UID:
324784
Concept ID:
C1837396
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. Different forms of CDGs can be recognized by altered isoelectric focusing (IEF) patterns of serum transferrin. For a general discussion of CDGs, see CDG Ia (212065) and CDG Ib (602579).
Congenital disorder of glycosylation type 1L
MedGen UID:
324794
Concept ID:
C1837438
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Cerebrofrontofacial syndrome
MedGen UID:
325262
Concept ID:
C1837819
Disease or Syndrome
Larsen-like syndrome
MedGen UID:
325280
Concept ID:
C1837884
Disease or Syndrome
Congenital disorder of glycosylation type 1K
MedGen UID:
332969
Concept ID:
C1837896
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Cleft palate, cardiac defect, genital anomalies, and ectrodactyly
MedGen UID:
324947
Concept ID:
C1838121
Disease or Syndrome
Brachydactyly-Mental Retardation syndrome
MedGen UID:
373895
Concept ID:
C1838126
Disease or Syndrome
2q37 microdeletion syndrome is characterized by mild-moderate developmental delay/intellectual disability, brachymetaphalangy of digits 3-5 (often digit 4 alone) (>50%), short stature, obesity, hypotonia, characteristic facial appearance, autism or autism spectrum disorder (30%), joint hypermobility/dislocation, and scoliosis. Other findings include seizures (20%-35%), congenital heart disease, CNS abnormalities (hydrocephalus, dilated ventricles), umbilical/inguinal hernia, tracheomalacia, situs abnormalities, gastrointestinal abnormalities, and renal malformations. Wilms tumor has been reported in two individuals.
Pectus excavatum, macrocephaly, short stature, dysplastic nails
MedGen UID:
373902
Concept ID:
C1838160
Disease or Syndrome
Aphalangia partial with syndactyly and duplication of metatarsal IV
MedGen UID:
324958
Concept ID:
C1838161
Disease or Syndrome
CODAS syndrome
MedGen UID:
333031
Concept ID:
C1838180
Disease or Syndrome
CODAS is an acronym for cerebral, ocular, dental, auricular, and skeletal anomalies. CODAS syndrome is a rare disorder characterized by a distinctive constellation of features that includes developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts (summary by Strauss et al., 2015).
Fryns macrocephaly
MedGen UID:
373933
Concept ID:
C1838281
Disease or Syndrome
Hydrocephalus, autosomal dominant
MedGen UID:
325006
Concept ID:
C1838347
Disease or Syndrome
Pachygyria with mental retardation and seizures
MedGen UID:
333107
Concept ID:
C1838491
Disease or Syndrome
This autosomal recessive neurodevelopmental disorder is characterized by pachygyria, mental retardation, seizures, and diffuse localization of arachnoid cysts. It most likely represents a neuronal migration disorder within the lissencephaly spectrum (summary by Guzel et al., 2007).
Pterygium colli mental retardation digital anomalies
MedGen UID:
374001
Concept ID:
C1838562
Disease or Syndrome
Male pseudohermaphroditism/mental retardation syndrome, Verloes type
MedGen UID:
325469
Concept ID:
C1838611
Disease or Syndrome
Puerto rican infant hypotonia syndrome
MedGen UID:
333148
Concept ID:
C1838651
Disease or Syndrome
Nivelon Nivelon Mabille syndrome
MedGen UID:
333149
Concept ID:
C1838654
Disease or Syndrome
Dwarfism, chondrodysplasia, pseudohermaphroditism, microcephaly, hypoplasia of the cerebellar vermis, and retinal retinal defects in association with skeletal, ocular, and other abnormalities. One of the two sisters in the original report was mentally retarded.
Hunter Rudd Hoffmann syndrome
MedGen UID:
374138
Concept ID:
C1839125
Congenital Abnormality
Trigonocephaly, short stature, and retarded psychomotor development.
Spastic paraplegia 2
MedGen UID:
374177
Concept ID:
C1839264
Disease or Syndrome
PLP1-related disorders of central nervous system myelin formation include a range of phenotypes from Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). PMD typically manifests in infancy or early childhood with nystagmus, hypotonia, and cognitive impairment; the findings progress to severe spasticity and ataxia. Life span is shortened. SPG2 manifests as spastic paraparesis with or without CNS involvement and usually normal life span. Intrafamilial variation of phenotypes can be observed, but the signs are usually fairly consistent within families. Female carriers may manifest mild to moderate signs of the disease.
Craniodigital syndrome - intellectual disability
MedGen UID:
333293
Concept ID:
C1839311
Disease or Syndrome
SCARF syndrome
MedGen UID:
326461
Concept ID:
C1839321
Disease or Syndrome
Prieto X-linked mental retardation syndrome
MedGen UID:
374294
Concept ID:
C1839730
Disease or Syndrome
Mental retardation syndrome with facial abnormalities, subcortical cerebral atrophy, defective tooth development, skin dimples at the lower back, lower limb defects, clinodactyly, luxation of the patella, and eye abnormalities.
Miles-Carpenter X-linked mental retardation syndrome
MedGen UID:
374295
Concept ID:
C1839735
Disease or Syndrome
Wilson-Turner X-linked mental retardation syndrome
MedGen UID:
333393
Concept ID:
C1839736
Disease or Syndrome
WTS is an X-linked neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males (summary by Harakalova et al., 2012).
Mental retardation and psoriasis
MedGen UID:
333408
Concept ID:
C1839801
Disease or Syndrome
Corpus callosum, partial agenesis of, X-linked
MedGen UID:
374339
Concept ID:
C1839909
Disease or Syndrome
L1 syndrome is an inherited disorder that primarily affects the nervous system. L1 syndrome involves a variety of features that were once thought to be distinct disorders, but are now considered to be part of the same syndrome. The most common characteristics of L1 syndrome are muscle stiffness (spasticity) of the lower limbs, intellectual disability, increased fluid in the center of the brain (hydrocephalus), and thumbs bent toward the palm (adducted thumbs). People with L1 syndrome can also have difficulty speaking (aphasia), seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum). The symptoms of L1 syndrome vary widely among affected individuals, even among members of the same family. Because this disorder involves spasticity of the lower limbs, L1 syndrome is sometimes referred to as spastic paraplegia type 1 (SPG1).
IFAP syndrome with or without BRESHECK syndrome
MedGen UID:
327007
Concept ID:
C1839988
Disease or Syndrome
The IFAP/BRESHECK syndrome is an X-linked multiple congenital anomaly disorder with variable severity. The classic triad, which defines IFAP, is ichthyosis follicularis, atrichia, and photophobia. Some patients have additional features, including mental retardation, brain anomalies, Hirschsprung disease, corneal opacifications, kidney dysplasia, cryptorchidism, cleft palate, and skeletal malformations, particularly of the vertebrae, which constitutes BRESHECK syndrome (summary by Naiki et al., 2012).
Single upper central incisor
MedGen UID:
326686
Concept ID:
C1840235
Disease or Syndrome
Hairy elbows
MedGen UID:
374773
Concept ID:
C1841696
Disease or Syndrome
Hairy elbows is a rare form of localized hypertrichosis. The lanugo type of hair usually appears in infancy, becomes coarser during early childhood, and regresses at adolescence (summary by Visser et al., 2002).
Gms syndrome
MedGen UID:
374804
Concept ID:
C1841854
Disease or Syndrome
Glomerulonephritis with sparse hair and telangiectases
MedGen UID:
374835
Concept ID:
C1841989
Disease or Syndrome
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome is an autosomal dominant disorder characterized by these 4 features, which begin in early childhood and are progressive (summary by Moalem et al., 2015).
Nablus mask-like facial syndrome
MedGen UID:
334165
Concept ID:
C1842464
Disease or Syndrome
Nablus mask-like facial syndrome (NMLFS) is a rare entity defined by distinctive facial features, including blepharophimosis, tight-appearing glistening facial skin, an abnormal hair pattern with an upswept frontal hairline, sparse arched eyebrows, flat and broad nose, long philtrum, distinctive ears, and a happy demeanor (summary by Jain et al., 2010).
Lipodystrophy, generalized, with mental retardation, deafness, short stature, and slender bones
MedGen UID:
334166
Concept ID:
C1842465
Disease or Syndrome
Dystonia 18
MedGen UID:
330866
Concept ID:
C1842534
Disease or Syndrome
The phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1-DS) is now known to be a continuum that includes the classic phenotype as well as dystonia 9, dystonia 18, atypical childhood absence epilepsy, myoclonic astatic epilepsy, and paroxysmal non-epileptic findings such as intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia. The classic phenotype is characterized by infantile-onset seizures, delayed neurologic development, acquired microcephaly, and complex movement disorders. Seizures begin before age two years in approximately 90% and later in approximately 10%. Several seizure types occur: generalized tonic or clonic, focal, myoclonic, atypical absence, atonic, and unclassified. The frequency, severity, and type of seizures vary among affected individuals and are not related to disease severity. Cognitive impairment, ranging from learning disabilities to severe intellectual disability, is typical. The complex movement disorder, characterized by ataxia, dystonia, and chorea, may occur in any combination and may be continuous, paroxysmal, or continuous with fluctuations in severity influenced by environmental factors such as fasting, fever, and intercurrent infection. Symptoms often improve substantially when a ketogenic diet is started.
Congenital disorder of glycosylation type 1J
MedGen UID:
334113
Concept ID:
C1842572
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Congenital disorder of glycosylation type 1I
MedGen UID:
334618
Concept ID:
C1842836
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Chromosome 1p36 deletion syndrome
MedGen UID:
334629
Concept ID:
C1842870
Disease or Syndrome
1p36 deletion syndrome is characterized by typical craniofacial features consisting of straight eyebrows, deeply set eyes, midface retrusion, wide and depressed nasal bridge, long philtrum, pointed chin, large, late-closing anterior fontanel (77%), microbrachycephaly (65%), epicanthal folds (50%), and posteriorly rotated, low-set, abnormal ears. Other characteristic findings include brachy/camptodactyly and short feet. Developmental delay/intellectual disability of variable degree are present in all, and hypotonia in 95%. Seizures occur in 44%-58% of affected individuals. Other findings include structural brain abnormalities (88%), congenital heart defects (71%), eye/vision problems (52%), hearing loss (47%), skeletal anomalies (41%), abnormalities of the external genitalia (25%), and renal abnormalities (22%).
Noonan-like syndrome with loose anagen hair
MedGen UID:
334697
Concept ID:
C1843181
Disease or Syndrome
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
MedGen UID:
375302
Concept ID:
C1843851
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. These phenotypes exemplify the diversity that can result from mutation of a given gene. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life up to about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, Parkinsonism, hypogonadism, and cataracts (in what has been called “chronic progressive external ophthalmoplegia plus,” or “CPEO+”).
Spinocerebellar ataxia 21
MedGen UID:
375311
Concept ID:
C1843891
Disease or Syndrome
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosomal locus) in which pathogenic variants occur.
Hypogonadism, male, with mental retardation and skeletal anomalies
MedGen UID:
334557
Concept ID:
C1843994
Disease or Syndrome
Hydrocephalus with cerebellar agenesis
MedGen UID:
375335
Concept ID:
C1844005
Disease or Syndrome
Oto-palato-digital syndrome, type II
MedGen UID:
337064
Concept ID:
C1844696
Congenital Abnormality
The otopalatodigital (OPD) spectrum disorders, characterized primarily by skeletal dysplasia, include the following: Otopalatodigital syndrome type I (OPD1). Otopalatodigital syndrome type II (OPD2). Frontometaphyseal dysplasia (FMD). Melnick-Needles syndrome (MNS). Terminal osseous dysplasia with pigmentary skin defects (TODPD). In OPD1, most manifestations are present at birth; females can present with severity similar to affected males, although some have only mild manifestations. In OPD2, females are less severely affected than related affected males. Most males with OPD2 die during the first year of life, usually from thoracic hypoplasia resulting in pulmonary insufficiency. Males who live beyond the first year of life are usually developmentally delayed and require respiratory support and assistance with feeding. In FMD, females are less severely affected than related affected males. Males do not experience progression of skeletal dysplasia but may have joint contractures and hand and foot malformations. Progressive scoliosis is observed in both affected males and females. In MNS, wide phenotypic variability is observed; some individuals are diagnosed in adulthood, while others require respiratory support and have reduced longevity. Prenatal lethality is most common in males with MNS. TODPD is a female limited condition, characterized by terminal skeletal dysplasia, pigmentary defects of the skin, and recurrent digital fibromata.
Charcot-Marie-Tooth disease, X-linked recessive, type 2
MedGen UID:
336803
Concept ID:
C1844873
Disease or Syndrome
Charcot-Marie-Tooth (CMT) hereditary neuropathy refers to a group of disorders characterized by a chronic motor and sensory polyneuropathy. The affected individual typically has distal muscle weakness and atrophy often associated with mild to moderate sensory loss, depressed tendon reflexes, and high-arched feet.
Arthrogryposis multiplex congenita, distal, X-linked
MedGen UID:
337123
Concept ID:
C1844934
Disease or Syndrome
X-linked infantile spinal muscular atrophy (XL-SMA) is characterized by congenital hypotonia and areflexia and evidence of degeneration and loss of anterior horn cells (i.e., lower motor neurons) in the spinal cord and brain stem. Often congenital contractures and/or fractures are present. Intellect is normal. Life span is shortened because of progressive ventilatory insufficiency resulting from chest muscle involvement.
Contractures ectodermal dysplasia cleft lip palate
MedGen UID:
375546
Concept ID:
C1844935
Disease or Syndrome
Spinocerebellar ataxia X-linked type 3
MedGen UID:
337124
Concept ID:
C1844936
Disease or Syndrome
A progressive disorder of the central nervous system characterized by ataxia, deafness, hypotonia, developmental delay, esotropia, and optic atrophy.
Microphthalmia syndromic 4
MedGen UID:
337127
Concept ID:
C1844948
Disease or Syndrome
Lenz microphthalmia syndrome (LMS) is characterized by unilateral or bilateral microphthalmia and/or clinical anophthalmia with malformations of the ears, teeth, fingers, skeleton, and/or genitourinary system. Microphthalmia is often accompanied by microcornea and glaucoma. Coloboma is present in approximately 60% of microphthalmic eyes with severity ranging from isolated iris coloboma to coloboma of the ciliary body, choroid, and optic disk. Ears may be low set, anteverted, posteriorly rotated, simple, cup shaped, or abnormally modeled. Hearing loss has been observed. Dental findings include irregularly shaped, missing, or widely spaced teeth. Duplicated thumbs, syndactyly, clinodactyly, camptodactyly, and microcephaly are common, as are narrow/sloping shoulders, underdeveloped clavicles, kyphoscoliosis, exaggerated lumbar lordosis, long cylindric thorax, and webbed neck. Genitourinary anomalies include hypospadias, cryptorchidism, renal hypoplasia/aplasia, and hydroureter. Approximately 60% of affected males have mild-to-severe intellectual disability or developmental delay.
Anemia sideroblastic and spinocerebellar ataxia
MedGen UID:
335078
Concept ID:
C1845028
Disease or Syndrome
X-linked sideroblastic anemia and ataxia (XLSA/A) is characterized by moderate anemia and early-onset spinocerebellar syndrome in males, manifest primarily as delayed walking, ataxia evident in early childhood, dysmetria, and dysdiadochokinesis. When present the intention tremor is mild and the dysarthria is mild to moderately severe. The ataxia has been described to be either non-progressive or slowly progressive. Upper motor neuron (UMN) signs in the legs, manifest by brisk deep tendon reflexes, unsustained ankle clonus, and equivocal or extensor plantar responses, are present in some males. Need for crutches or a wheelchair has been reported. Strabismus is seen in some males. Nystagmus and hypometric saccades may occur. Mild learning disability and depression are seen. The moderate hypochromic and microcytic anemia does not cause symptoms. Carrier (heterozygous) females have a normal neurologic examination and may show mild hematologic abnormalities.
ATR-X syndrome
MedGen UID:
337145
Concept ID:
C1845055
Disease or Syndrome
Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome is characterized by distinctive craniofacial features, genital anomalies, severe developmental delays, hypotonia, intellectual disability, and mild-to-moderate anemia secondary to alpha-thalassemia. Craniofacial abnormalities include small head circumference, telecanthus or widely spaced eyes, short nose, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip with coarsening of the facial features over time. Although all affected individuals have a normal 46,XY karyotype, genital anomalies range from hypospadias and undescended testicles to severe hypospadias and ambiguous genitalia, to normal-appearing female external genitalia. Global developmental delays are evident in infancy and some affected individuals never walk independently or develop significant speech.
Chromosome Xp11.3 deletion syndrome
MedGen UID:
336862
Concept ID:
C1845136
Disease or Syndrome
Dent disease 2
MedGen UID:
336867
Concept ID:
C1845167
Disease or Syndrome
Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and chronic kidney disease (CKD). Males younger than age ten years may manifest only low molecular-weight (LMW) proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. Rickets or osteomalacia are occasionally observed, and mild short stature, although underappreciated, may be a common occurrence. Disease severity can vary within the same family. Males with Dent disease 2 (caused by mutation of OCRL) are at increased risk for intellectual disability. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely if ever develop CKD.
Heterotopia, periventricular, Ehlers-Danlos variant
MedGen UID:
375610
Concept ID:
C1845235
Disease or Syndrome
Periventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means "out of place." In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles. Periventricular heterotopia usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Difficulty with reading and spelling (dyslexia) has been reported in some people with periventricular heterotopia. Less commonly, individuals with periventricular heterotopia may have more severe brain malformations, small head size (microcephaly), developmental delays, recurrent infections, blood vessel abnormalities, or other problems. Periventricular heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels.
Mental retardation, syndromic, Claes-Jensen type, X-linked
MedGen UID:
335139
Concept ID:
C1845243
Disease or Syndrome
Martin-Probst deafness-mental retardation syndrome
MedGen UID:
375620
Concept ID:
C1845285
Disease or Syndrome
Epilepsy, X-linked, with variable learning disabilities and behavior disorders
MedGen UID:
337214
Concept ID:
C1845343
Disease or Syndrome
Mental retardation X-linked with cerebellar hypoplasia and distinctive facial appearance
MedGen UID:
336920
Concept ID:
C1845366
Disease or Syndrome
Corpus callosum, agenesis of, with mental retardation, ocular coloboma, and micrognathia
MedGen UID:
335185
Concept ID:
C1845446
Disease or Syndrome
Cubitus valgus with mental retardation and unusual facies
MedGen UID:
336943
Concept ID:
C1845450
Disease or Syndrome
Congenital bilateral perisylvian syndrome
MedGen UID:
337000
Concept ID:
C1845668
Congenital Abnormality
Polymicrogyria (PMG) is a malformation of cortical development in which the brain surface is irregular and the normal gyral pattern replaced by multiple small, partly fused gyri separated by shallow sulci. Microscopic examination shows a simplified 4-layered or unlayered cortex. Several patterns of PMG, including bilateral frontal, bilateral perisylvian, and bilateral mesial occipital PMG, have been described on the basis of their topographic distribution. All but the perisylvian form appear to be rare. Bilateral perisylvian PMG (BPP) often results in a typical clinical syndrome that is manifested by mild mental retardation, epilepsy, and pseudobulbar palsy, which causes difficulties with expressive speech and feeding (Kuzniecky et al., 1993). PMG may be a feature of other conditions as well (see, e.g., 300643).
MENTAL RETARDATION, X-LINKED, WITH SHORT STATURE (disorder)
MedGen UID:
375754
Concept ID:
C1845845
Disease or Syndrome
Syndromic X-linked mental retardation, Cabezas type
MedGen UID:
337334
Concept ID:
C1845861
Disease or Syndrome
This form of syndromic X-linked mental retardation is characterized primarily by short stature, hypogonadism, and abnormal gait, with other more variable features such as speech delay, prominent lower lip, and tremor (Cabezas et al., 2000).
Creatine deficiency, X-linked
MedGen UID:
337451
Concept ID:
C1845862
Disease or Syndrome
The cerebral creatine deficiency syndromes (CCDS), inborn errors of creatine metabolism, include the two creatine biosynthesis disorders, guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT or GATM) deficiency, and the creatine transporter (SLC6A8) deficiency. Intellectual disability and seizures are common to all three CCDS. The majority of individuals with GAMT deficiency have a behavior disorder that can include autistic behaviors and self-mutilation; a significant proportion have pyramidal/extrapyramidal findings. Onset is between ages three months and three years. Only seven individuals with AGAT deficiency have been reported. The phenotype of SLC6A8 deficiency in affected males ranges from mild intellectual disability and speech delay to severe intellectual disability, seizures, and behavior disorder; age at diagnosis ranges from two to 66 years. Females heterozygous for SLC6A8 deficiency may have learning and behavior problems.
Adrenomyodystrophy
MedGen UID:
337494
Concept ID:
C1846044
Disease or Syndrome
Siderius X-linked mental retardation syndrome
MedGen UID:
337375
Concept ID:
C1846055
Disease or Syndrome
X-linked intellectual disability, Siderius type is a condition characterized by mild to moderate intellectual disability that affects only males. Affected boys often have delayed development of motor skills such as walking, and their speech may be delayed. Individuals with X-linked intellectual disability, Siderius type frequently also have an opening in the lip (cleft lip) with an opening in the roof of the mouth (cleft palate). A cleft can occur on one or both sides of the upper lip. Some boys and men with this condition have distinctive facial features, including a long face, a sloping forehead, a broad nasal bridge, a prominent bone in the lower forehead (supraorbital ridge), and outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may also have low-set ears and large hands.
Abidi X-linked mental retardation syndrome
MedGen UID:
337376
Concept ID:
C1846056
Disease or Syndrome
Armfield X-linked mental retardation syndrome
MedGen UID:
375800
Concept ID:
C1846057
Disease or Syndrome
Mental retardation X-linked syndromic 11
MedGen UID:
335348
Concept ID:
C1846145
Disease or Syndrome
Mental retardation, X-linked, syndromic 10
MedGen UID:
335353
Concept ID:
C1846168
Disease or Syndrome
Mental retardation X-linked syndromic 7
MedGen UID:
337403
Concept ID:
C1846170
Disease or Syndrome
Lissencephaly 2, X-linked
MedGen UID:
375832
Concept ID:
C1846171
Disease or Syndrome
X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype (Bonneau et al., 2002). LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Amme complex
MedGen UID:
337424
Concept ID:
C1846242
Disease or Syndrome
Oculofaciocardiodental syndrome
MedGen UID:
337547
Concept ID:
C1846265
Disease or Syndrome
Lenz microphthalmia syndrome (LMS) is characterized by unilateral or bilateral microphthalmia and/or clinical anophthalmia with malformations of the ears, teeth, fingers, skeleton, and/or genitourinary system. Microphthalmia is often accompanied by microcornea and glaucoma. Coloboma is present in approximately 60% of microphthalmic eyes with severity ranging from isolated iris coloboma to coloboma of the ciliary body, choroid, and optic disk. Ears may be low set, anteverted, posteriorly rotated, simple, cup shaped, or abnormally modeled. Hearing loss has been observed. Dental findings include irregularly shaped, missing, or widely spaced teeth. Duplicated thumbs, syndactyly, clinodactyly, camptodactyly, and microcephaly are common, as are narrow/sloping shoulders, underdeveloped clavicles, kyphoscoliosis, exaggerated lumbar lordosis, long cylindric thorax, and webbed neck. Genitourinary anomalies include hypospadias, cryptorchidism, renal hypoplasia/aplasia, and hydroureter. Approximately 60% of affected males have mild-to-severe intellectual disability or developmental delay.
Mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity
MedGen UID:
375855
Concept ID:
C1846278
Disease or Syndrome
Juvenile-onset dystonia
MedGen UID:
339494
Concept ID:
C1846331
Disease or Syndrome
Spinocerebellar ataxia 19
MedGen UID:
339504
Concept ID:
C1846367
Disease or Syndrome
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosomal locus) in which pathogenic variants occur.
Focal cortical dysplasia of Taylor
MedGen UID:
339510
Concept ID:
C1846385
Disease or Syndrome
Cortical dysplasia of Taylor is a cerebral developmental malformation that results in a clinical phenotype of intractable epilepsy usually requiring surgery. FCDT has been classified histologically into 2 subtypes: a type without balloon cells, known as type IIA, and a type with balloon cells, known as type IIB (Palmini et al., 2004).
Lathosterolosis
MedGen UID:
375885
Concept ID:
C1846421
Disease or Syndrome
Gaze palsy, familial horizontal, with progressive scoliosis
MedGen UID:
339538
Concept ID:
C1846496
Disease or Syndrome
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a disorder that affects vision and also causes an abnormal curvature of the spine (scoliosis). People with this condition are unable to move their eyes side-to-side (horizontally). As a result, affected individuals must turn their head instead of moving their eyes to track moving objects. Up-and-down (vertical) eye movements are typically normal. In people with HGPPS, an abnormal side-to-side curvature of the spine develops in infancy or childhood. It tends to be moderate to severe and worsens over time. Because the abnormal spine position can be painful and interfere with movement, it is often treated with surgery early in life.
Amish lethal microcephaly
MedGen UID:
375938
Concept ID:
C1846648
Disease or Syndrome
Amish lethal microcephaly is characterized by microcephaly and early death. The occipitofrontal circumference is typically six to 12 standard deviations below the mean; anterior and posterior fontanels are closed at birth and facial features are distorted. The average life span is between five and six months.
Congenital disorder of glycosylation type 1G
MedGen UID:
375947
Concept ID:
C1846695
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Lig4 syndrome
MedGen UID:
339855
Concept ID:
C1847827
Disease or Syndrome
PHACE syndrome
MedGen UID:
376231
Concept ID:
C1847874
Disease or Syndrome
PHACE is an acronym for a neurocutaneous syndrome encompassing the following features: posterior fossa brain malformations, hemangiomas of the face (large or complex), arterial anomalies, cardiac anomalies, and eye abnormalities. The association is referred to as PHACES when ventral developmental defects, such as sternal clefting or supraumbilical raphe, are present (summary by Bracken et al., 2011).
Hypotonia-cystinuria syndrome
MedGen UID:
341133
Concept ID:
C1848030
Disease or Syndrome
Lissencephaly, X-linked
MedGen UID:
336286
Concept ID:
C1848199
Disease or Syndrome
DCX-related disorders include the neuronal migration disorders classic lissencephaly (formerly also known as lissencephaly type 1), usually in males; and subcortical band heterotopia (SBH, also called double cortex), primarily in females. Males with classic DCX-related lissencephaly typically have severe and global developmental delay, infantile-onset seizures (infantile spasms, West syndrome, focal and generalized seizures), and severe intellectual disability. In individuals with SBH, cognitive abilities range from normal to learning disabilities and/or severe intellectual disability. The majority of individuals with SBH present with focal or generalized seizures. Behavior problems may also be observed. In DCX-related lissencephaly and SBH the severity of the clinical manifestation correlates with the degree of the underlying brain malformation.
Hyde Forster Mccarthy Berry syndrome
MedGen UID:
341171
Concept ID:
C1848205
Disease or Syndrome
Zunich neuroectodermal syndrome
MedGen UID:
341214
Concept ID:
C1848392
Disease or Syndrome
Zunich neuroectodermal syndrome is an extremely rare autosomal recessive multisystem disorder clinically characterized by colobomas, congenital heart defects, migratory ichthyosiform dermatosis, mental retardation, and ear anomalies (CHIME). Other clinical features include distinctive facial features, abnormal growth, genitourinary abnormalities, seizures, and feeding difficulties (summary by Ng et al., 2012).
Mental retardation Wolff type
MedGen UID:
336345
Concept ID:
C1848439
Disease or Syndrome
Methylmalonic acidemia with homocystinuria cblD
MedGen UID:
341253
Concept ID:
C1848552
Disease or Syndrome
The clinical manifestations of disorders of intracellular cobalamin metabolism can be highly variable even within a single complementation group. The prototype and best understood is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range, including: Newborns, who can have intrauterine growth retardation (IUGR) and microcephaly; Infants, who can have poor feeding, failure to thrive, pallor, and neurologic signs, and occasionally hemolytic uremic syndrome (HUS) and/or seizures including infantile spasms; Toddlers, who can have failure to thrive, poor head growth, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures; and Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, and/or subacute combined degeneration of the spinal cord.
Ulnar hypoplasia with mental retardation
MedGen UID:
341275
Concept ID:
C1848650
Disease or Syndrome
Teebi syndrome
MedGen UID:
341296
Concept ID:
C1848743
Disease or Syndrome
Trichomegaly with mental retardation, dwarfism and pigmentary degeneration of retina
MedGen UID:
338532
Concept ID:
C1848745
Congenital Abnormality
Oliver-McFarlane syndrome is a rare congenital disorder characterized by trichomegaly, severe chorioretinal atrophy and multiple pituitary hormone deficiencies, including growth hormone (GH; 139250), gonadotropins (see 118860), and thyroid-stimulating hormone (TSH; see 118850). Thyroid and GH abnormalities may be present at birth and, if untreated, result in intellectual impairment and profound short stature. Congenital hypogonadism occurs in half of patients, and nearly all have documented hypogonadotropic hypogonadism during puberty, with subsequent reproductive dysfunction. Chorioretinal atrophy is typically noted in the first 5 years of life. Half of reported cases have spinocerebellar involvement, including ataxia, spastic paraplegia, and peripheral neuropathy (summary by Hufnagel et al., 2015). Laurence-Moon syndrome (245800) is an allelic disorder with overlapping features.
Thumb, hypoplastic, with choroid coloboma, poorly developed antihelix, and deafness
MedGen UID:
376448
Concept ID:
C1848816
Disease or Syndrome
Thoracic dysplasia-hydrocephalus syndrome
MedGen UID:
338562
Concept ID:
C1848864
Disease or Syndrome
Tapetoretinal degeneration with ataxia
MedGen UID:
336461
Concept ID:
C1848932
Disease or Syndrome
Cold-induced sweating syndrome 1
MedGen UID:
338577
Concept ID:
C1848947
Disease or Syndrome
Crisponi syndrome, the infantile presentation of cold-induced sweating syndrome (CISS), is characterized by dysmorphic features (distinctive facies, lower facial weakness, flexion deformity at the elbows, camptodactyly with fisted hands, misshapen feet, and overriding toes), poor suck reflex and severely impaired swallowing, temperature spikes not associated with infections, and increased risk for seizures and sudden death. During the first decade of life, children with CISS develop profuse sweating of the face, arms, and chest with ambient temperatures below 18º to 22º C and often with other stimuli including apprehension or ingestion of sweets. Affected individuals sweat very little in hot environments and may feel overheated. In the second decade, progressive thoracolumbar kyphoscoliosis requires intervention.
Spinocerebellar degeneration and corneal dystrophy
MedGen UID:
341379
Concept ID:
C1849087
Disease or Syndrome
Spinocerebellar ataxia with dysmorphism
MedGen UID:
336495
Concept ID:
C1849088
Disease or Syndrome
Spastic quadriplegia retinitis pigmentosa mental retardation
MedGen UID:
376519
Concept ID:
C1849112
Disease or Syndrome
Quadriplegia in association with mental retardation, retinitis pigmentosa, and impaired hearing.
Spastic paresis, glaucoma, and mental retardation
MedGen UID:
376520
Concept ID:
C1849113
Disease or Syndrome
Spastic diplegia infantile type
MedGen UID:
376526
Concept ID:
C1849139
Disease or Syndrome
Insulin-like growth factor 1 resistance to
MedGen UID:
338622
Concept ID:
C1849157
Disease or Syndrome
Schinzel-Giedion syndrome
MedGen UID:
341423
Concept ID:
C1849294
Disease or Syndrome
Schinzel-Giedion syndrome is a highly recognizable syndrome characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, and cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia (summary by Hoischen et al., 2010).
Rodrigues blindness
MedGen UID:
340297
Concept ID:
C1849332
Disease or Syndrome
Robinow syndrome, autosomal recessive
MedGen UID:
341431
Concept ID:
C1849334
Disease or Syndrome
Autosomal recessive Robinow syndrome is a severe skeletal dysplasia characterized by dysmorphic facial features, including frontal bossing, hypertelorism, and broad nose, short-limbed dwarfism, vertebral segmentation, and genital hypoplasia (summary by van Bokhoven et al., 2000). Genetic Heterogeneity of Robinow Syndrome See also autosomal dominant Robinow syndrome-1 (DRS1; 180700), caused by mutation in the WNT5A gene (164975) on chromosome 3p, and DRS2 (616331), caused by mutation in the DVL1 gene (601365) on chromosome 1p36.
Rhizomelic syndrome
MedGen UID:
376574
Concept ID:
C1849382
Disease or Syndrome
Retinohepatoendocrinologic syndrome
MedGen UID:
340315
Concept ID:
C1849399
Disease or Syndrome
Retinitis pigmentosa, deafness, mental retardation, and hypogonadism
MedGen UID:
340317
Concept ID:
C1849401
Disease or Syndrome
Renal dysplasia, retinal pigmentary dystrophy, cerebellar ataxia and skeletal dysplasia
MedGen UID:
341455
Concept ID:
C1849437
Disease or Syndrome
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Radioulnar synostosis, unilateral, with developmental retardation and hypotonia
MedGen UID:
341460
Concept ID:
C1849470
Disease or Syndrome
Pyridoxine-dependent epilepsy
MedGen UID:
340341
Concept ID:
C1849508
Disease or Syndrome
Pyridoxine-dependent epilepsy is characterized by intractable seizures that are not controlled with antiepileptic drugs but that respond both clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). Multiple types of clinical seizures have been reported in individuals with pyridoxine-dependent epilepsy. Dramatic presentations consisting of prolonged seizures and recurrent episodes of status epilepticus are typical; recurrent self-limited events including partial seizures, generalized seizures, atonic seizures, myoclonic events, and infantile spasms also occur. Affected individuals may have electrographic seizures without clinical correlates. Infants with the classic neonatal presentation begin to experience seizures soon after birth. Atypical features include: late-onset seizures (age =3 years); seizures that initially respond to antiepileptic drugs and then become intractable; seizures during early life that do not respond to pyridoxine but that are then controlled with pyridoxine several months later; and prolonged seizure-free intervals (=5 1/2 months) that occur after pyridoxine discontinuation. Intellectual disability is common.
Pseudoneonatal adrenoleukodystrophy
MedGen UID:
376636
Concept ID:
C1849678
Disease or Syndrome
Peroxisomal acyl-CoA oxidase deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also D-bifunctional protein deficiency (261515), caused by mutation in the HSD17B4 gene (601860) on chromosome 5q2. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (see 601539) (Watkins et al., 1995).
Popliteal pterygium syndrome lethal type
MedGen UID:
337894
Concept ID:
C1849718
Disease or Syndrome
Bartsocas-Papas syndrome (lethal popliteal pterygium syndrome) is an autosomal recessive disorder characterized by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly. Early lethality is common, although survival into childhood and beyond has been reported (summary by Mitchell et al., 2012). A less severe form of popliteal pterygium syndrome (119500) is caused by mutation in the IRF6 gene (607199).
Polyglucosan body disease, adult
MedGen UID:
342338
Concept ID:
C1849722
Disease or Syndrome
Adult polyglucosan body disease (APBD) is characterized by adult-onset progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, and mild cognitive difficulties (often executive dysfunction).
Pilodental dysplasia with refractive errors
MedGen UID:
376661
Concept ID:
C1849805
Disease or Syndrome
Pili torti developmental delay neurological abnormalities
MedGen UID:
342358
Concept ID:
C1849811
Disease or Syndrome
Pellagra like syndrome
MedGen UID:
337955
Concept ID:
C1850052
Disease or Syndrome
PEHO syndrome
MedGen UID:
342404
Concept ID:
C1850055
Disease or Syndrome
Otoonychoperoneal syndrome
MedGen UID:
376704
Concept ID:
C1850105
Disease or Syndrome
Osteopenia and sparse hair
MedGen UID:
337979
Concept ID:
C1850140
Disease or Syndrome
Osteolysis syndrome recessive
MedGen UID:
376714
Concept ID:
C1850143
Disease or Syndrome
Omodysplasia 1
MedGen UID:
340513
Concept ID:
C1850318
Disease or Syndrome
Omodysplasia-1 (OMOD1) is a rare autosomal recessive skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Typical facial features include a prominent forehead, frontal bossing, short nose with a depressed broad bridge, short columella, anteverted nostrils, long philtrum, and small chin. Variable findings are cryptorchidism, hernias, congenital heart defects, and cognitive delay (Elcioglu et al., 2004; Albano et al., 2007). Genetic Heterogeneity of Omodysplasia In an autosomal dominant form of omodysplasia (OMOD2; 164745), abnormalities are limited to the upper limbs. The facial changes and typical growth defect of the distal humerus with complex deformity of the elbows appear to be similar in both entities (Baxova et al., 1994).
Oliver syndrome
MedGen UID:
342472
Concept ID:
C1850320
Disease or Syndrome
Oculorenocerebellar syndrome
MedGen UID:
340516
Concept ID:
C1850331
Disease or Syndrome
Oculopalatocerebral syndrome
MedGen UID:
338025
Concept ID:
C1850338
Disease or Syndrome
Oculopalatocerebral syndrome is a rare disorder characterized by low birth weight, microcephaly, persistent hyperplastic primary vitreous, microphthalmia, large ears, small hands and feet, cleft palate, joint hypermobility, developmental delay, and cerebral atrophy (summary by Pellegrino et al., 2001).
Oculocerebral hypopigmentation syndrome of preus
MedGen UID:
342477
Concept ID:
C1850340
Disease or Syndrome
Elejalde disease
MedGen UID:
342508
Concept ID:
C1850466
Disease or Syndrome
Nakajo syndrome
MedGen UID:
376827
Concept ID:
C1850568
Disease or Syndrome
This autosomal recessive systemic autoinflammatory disorder is characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions.
Nasodigitoacoustic syndrome
MedGen UID:
338088
Concept ID:
C1850627
Disease or Syndrome
Keipert syndrome is characterized by brachydactyly, broad thumbs and halluces, hypertelorism and other minor facial dysmorphic features, and sensorineural deafness. Phenotypically related syndromes include Teunissen-Cremers syndrome (184460), Muenke syndrome (602849) and Keutel syndrome (245150) (Nik-Zainal et al., 2008).
Myotonia with skeletal abnormalities and mental retardation
MedGen UID:
342557
Concept ID:
C1850654
Disease or Syndrome
Congenital nonprogressive myopathy with Moebius and Robin sequences
MedGen UID:
338115
Concept ID:
C1850746
Disease or Syndrome
Laurin-Sandrow syndrome
MedGen UID:
340697
Concept ID:
C1851100
Disease or Syndrome
Gingival fibromatosis with hypertrichosis
MedGen UID:
342675
Concept ID:
C1851120
Disease or Syndrome
Extreme hirsutism with gingival fibromatosis follows a dominant pattern of inheritance (Weski, 1920; Garn and Hatch, 1950). There is no necessary relationship between the age of development of the gingival changes and the hypertrichosis. The latter may be present at birth but often appears at puberty (Anderson et al., 1969). For a discussion of genetic heterogeneity of congenital generalized hypertrichosis, see HTC1 (145701).
Extrasystoles, multiform ventricular, with short stature, hyperpigmentation and microcephaly
MedGen UID:
343564
Concept ID:
C1851412
Disease or Syndrome
Lehman syndrome
MedGen UID:
342070
Concept ID:
C1851710
Disease or Syndrome
Craniosynostosis, sagittal, with Dandy-Walker malformation and hydrocephalus
MedGen UID:
342248
Concept ID:
C1852488
Disease or Syndrome
Corneal hypesthesia with retinal abnormalities, sensorineural deafness, unusual facies, persistent ductus arteriosus, and mental retardation
MedGen UID:
342261
Concept ID:
C1852543
Disease or Syndrome
Coloboma, uveal, with cleft lip and palate and mental retardation
MedGen UID:
342303
Concept ID:
C1852750
Disease or Syndrome
22q13.3 deletion syndrome
MedGen UID:
339994
Concept ID:
C1853490
Disease or Syndrome
Phelan-McDermid syndrome (22q13.3 deletion syndrome) is characterized by neonatal hypotonia, global developmental delay, absent to severely delayed speech, and normal to accelerated growth. Most individuals have moderate to profound intellectual disability. Other features include large fleshy hands, dysplastic toenails, and decreased perspiration that results in a tendency to overheat. Behavior characteristics include mouthing or chewing non-food items, decreased perception of pain, and autistic-like affect.
Genitopatellar syndrome
MedGen UID:
381208
Concept ID:
C1853566
Disease or Syndrome
Genitopatellar syndrome is a rare disorder consisting of microcephaly, severe psychomotor retardation, and characteristic coarse facial features, including broad nose and small or retracted chin, associated with congenital flexion contractures of the lower extremities, abnormal or missing patellae, and urogenital anomalies (summary by Penttinen et al., 2009). The SBBYS variant of Ohdo syndrome (603736) is an allelic disorder with overlapping features.
Spondyloocular syndrome, autosomal recessive
MedGen UID:
343011
Concept ID:
C1853925
Disease or Syndrome
Cerebrooculonasal syndrome
MedGen UID:
340138
Concept ID:
C1854108
Disease or Syndrome
Mesomelic dysplasia Savarirayan type
MedGen UID:
343129
Concept ID:
C1854470
Disease or Syndrome
Chudley Rozdilsky syndrome
MedGen UID:
381471
Concept ID:
C1854663
Disease or Syndrome
Mitochondrial complex II deficiency
MedGen UID:
344401
Concept ID:
C1855008
Disease or Syndrome
Complex II, also known as succinate dehydrogenase (EC 1.3.5.1), is part of the mitochondrial respiratory chain. Deficiency of complex II is characterized by highly variable phenotypic expression.
Say Barber Miller syndrome
MedGen UID:
343258
Concept ID:
C1855078
Disease or Syndrome
Winship Viljoen Leary syndrome
MedGen UID:
381554
Concept ID:
C1855080
Disease or Syndrome
Severe microcephaly and self-limiting dilated cardiomyopathy (which improved later in childhood) associated with delayed development and mildly dysmorphic facies..
Primary autosomal recessive microcephaly 1
MedGen UID:
344415
Concept ID:
C1855081
Disease or Syndrome
Primary autosomal recessive microcephalies (MCPH) and Seckel syndrome (SCKS) spectrum disorders are characterized by microcephaly and the absence of visceral malformations. Although MCHP and SCKS were previously distinguished by height (maximum height in SCKS was equivalent to the minimum height in MCPH), stature is no longer a discriminating feature, leading to the conclusion that these phenotypes constitute a spectrum rather than distinct entities. Microcephaly is characterized by: Onset during the second trimester of gestation; Occipito-frontal head circumference (OFC) at birth equal to or less than -2 SD below the mean for sex, age, and ethnicity; Slower than average increase in OFC after birth. Variable findings in the MCPH-SCKS spectrum disorders include: Brain structure (which is normal in the majority); Degree of cognitive impairment (usually mild to moderate without significant motor delay in the majority of persons with MCPH and more severe in those with SCKS and MCPH with brain malformations); Degree of short stature; Craniosynostosis (which may be secondary to poor brain growth).
Microcephalic primordial dwarfism Toriello type
MedGen UID:
381556
Concept ID:
C1855089
Disease or Syndrome
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
MedGen UID:
344424
Concept ID:
C1855114
Disease or Syndrome
Isolated methylmalonic acidemia/aciduria is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut(0) enzymatic subtype or mut(–) enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD variant 2 type), or deficiency of the enzyme methylmalonyl-CoA epimerase. Onset of the manifestations of isolated methylmalonic acidemia/aciduria ranges from the neonatal period to adulthood. All phenotypes demonstrate periods of relative health and intermittent metabolic decompensation, usually associated with intercurrent infections and stress. In the neonatal period the disease can present with lethargy, vomiting, hypotonia, hypothermia, respiratory distress, severe ketoacidosis, hyperammonemia, neutropenia, and thrombocytopenia and can result in death. In the infantile/non-B12-responsive phenotype, the most common form, infants are normal at birth but develop lethargy, vomiting, dehydration, hepatomegaly, hypotonia, and encephalopathy. An intermediate B12-responsive phenotype can occasionally present in neonates, but usually presents in the first months or years of life; affected children exhibit anorexia, failure to thrive, hypotonia, and developmental delay, and sometimes have protein aversion and/or vomiting and lethargy after protein intake. Atypical and "benign"/adult methylmalonic acidemia are associated with increased, albeit mild, urinary excretion of methylmalonate; however, it is uncertain if some of these individuals will develop symptoms. Major secondary complications of methylmalonic acidemia include developmental delay (variable); tubulointerstitial nephritis with progressive renal failure; “metabolic stroke” (acute and chronic basal ganglia involvement); disabling movement disorder with choreoathetosis, dystonia, and para/quadriparesis; pancreatitis; growth failure; functional immune impairment; and optic nerve atrophy.
3-methylglutaconic aciduria type IV
MedGen UID:
344425
Concept ID:
C1855126
Disease or Syndrome
The category of 3-methylglutaconic aciduria type IV (MGCA4) represents a heterogeneous unclassified group of patients who share mild or intermittent urinary excretion of 3-methylglutaconic acid. MGCA excretion is a nonspecific finding observed in many other disorders caused by defects in mitochondrial energy metabolism (Gunay-Aygun, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA1 (250950)
Metaphyseal dysostosis mental retardation conductive deafness
MedGen UID:
344437
Concept ID:
C1855175
Disease or Syndrome
Metaphyseal acroscyphodysplasia
MedGen UID:
344453
Concept ID:
C1855243
Disease or Syndrome
Mental retardation syndrome, Belgian type
MedGen UID:
343317
Concept ID:
C1855303
Disease or Syndrome
Marfanoid mental retardation syndrome, autosomal
MedGen UID:
343326
Concept ID:
C1855347
Disease or Syndrome
Marfanoid habitus with microcephaly and glomerulonephritis
MedGen UID:
343327
Concept ID:
C1855348
Disease or Syndrome
A syndrome marked by marfanoid habitus (tall stature with long and slim limbs, little subcutaneous fat, arachnodactyly, joint hyperextensibility, narrow face, small chin, large testes, and hypotonia) associated with microcephaly and glomerulonephritis.
Limb deficiencies distal with micrognathia
MedGen UID:
343368
Concept ID:
C1855500
Disease or Syndrome
Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM3 have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting (Elliott and Evans, 2006). For additional phenotypic information and a discussion of genetic heterogeneity in this disorder, see SHFM1 (183600).
Limb defects, distal transverse, with mental retardation and spasticity
MedGen UID:
340888
Concept ID:
C1855501
Disease or Syndrome
Leukomelanoderma, infantilism, mental retardation, hypodontia, hypotrichosis
MedGen UID:
383698
Concept ID:
C1855504
Disease or Syndrome
Lambert syndrome
MedGen UID:
343381
Concept ID:
C1855551
Disease or Syndrome
Keutel syndrome
MedGen UID:
383722
Concept ID:
C1855607
Disease or Syndrome
Keutal syndrome is an autosomal recessive disorder characterized by multiple peripheral pulmonary stenoses, brachytelephalangy, inner ear deafness, and abnormal cartilage ossification or calcification (summary by Khosroshahi et al., 2014).
Kaufman oculocerebrofacial syndrome
MedGen UID:
343403
Concept ID:
C1855663
Disease or Syndrome
Absent corpus callosum cataract immunodeficiency
MedGen UID:
340962
Concept ID:
C1855772
Disease or Syndrome
Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum, cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy (summary by Finocchi et al., 2012).
Ichthyosis, mental retardation, dwarfism and renal impairment
MedGen UID:
340966
Concept ID:
C1855787
Disease or Syndrome
Ichthyosis alopecia eclabion ectropion mental retardation
MedGen UID:
344577
Concept ID:
C1855788
Disease or Syndrome
Bamforth syndrome
MedGen UID:
343420
Concept ID:
C1855794
Disease or Syndrome
Hypoparathyroidism retardation dysmorphism syndrome
MedGen UID:
340984
Concept ID:
C1855840
Disease or Syndrome
Hypomandibular faciocranial dysostosis
MedGen UID:
343427
Concept ID:
C1855848
Disease or Syndrome
Hypomandibular faciocranial syndrome consists of craniosynostosis, prominent eyes, deficient midface and zygomatic arches, short nose with anteverted nares, protruding lower face, minute oral aperture, persistent buccopharyngeal membrane, severe mandibular hypoplasia, and various extracephalic anomalies (summary by Gorlin et al., 2001).
Hydroxylysinuria
MedGen UID:
343450
Concept ID:
C1855986
Disease or Syndrome
L-2-hydroxyglutaric aciduria
MedGen UID:
341029
Concept ID:
C1855995
Disease or Syndrome
2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA). The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I. L-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood. Combined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood.
Homocystinuria-Megaloblastic anemia due to defect in cobalamin metabolism, cblE complementation type
MedGen UID:
344640
Concept ID:
C1856057
Disease or Syndrome
The clinical manifestations of disorders of intracellular cobalamin metabolism can be highly variable even within a single complementation group. The prototype and best understood is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range, including: Newborns, who can have intrauterine growth retardation (IUGR) and microcephaly; Infants, who can have poor feeding, failure to thrive, pallor, and neurologic signs, and occasionally hemolytic uremic syndrome (HUS) and/or seizures including infantile spasms; Toddlers, who can have failure to thrive, poor head growth, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures; and Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, and/or subacute combined degeneration of the spinal cord.
HISTIDINURIA DUE TO A RENAL TUBULAR DEFECT
MedGen UID:
344651
Concept ID:
C1856097
Disease or Syndrome
Hirschsprung disease with polydactyly, renal agenesis, and deafness
MedGen UID:
341066
Concept ID:
C1856112
Disease or Syndrome
Mowat-Wilson syndrome
MedGen UID:
341067
Concept ID:
C1856113
Disease or Syndrome
Mowat-Wilson syndrome (MWS) is characterized by the following: Distinctive facial features. Structural anomalies including: Hirschsprung disease. Genitourinary anomalies (particularly hypospadias in males). Congenital heart defects (particularly abnormalities of the pulmonary arteries and/or valves). Agenesis or hypogenesis of the corpus callosum. Eye defects (microphthalmia and Axenfeld anomaly). Functional differences including: Moderate to severe intellectual disability. Severe speech impairment with relative preservation of receptive language. Seizures. Growth retardation with microcephaly. Chronic constipation in those without Hirschsprung disease.
Isolated hemihyperplasia
MedGen UID:
383853
Concept ID:
C1856184
Disease or Syndrome
Isolated hemihyperplasia is an abnormality of cell proliferation leading to asymmetric overgrowth of one or more regions of the body. The term 'hemihyperplasia' has replaced the term 'hemihypertrophy' to describe accurately the increase in cell number found in these patients. The incidence of isolated hemihyperplasia is estimated to be 1 in 86,000. Idiopathic hemihypertrophy is associated with increased risk of embryonal cancers in childhood, particularly Wilms tumor (194070) (Shuman et al., 2006). Hoyme et al. (1998) provided an anatomic classification of hemihyperplasia: complex hemihyperplasia is involvement of half of the body, including at least 1 arm and 1 leg; affected parts may be contralateral or ipsilateral. Simple hemihyperplasia is involvement of a single limb. See also facial hemihyperplasia (133900). Although isolated hemihyperplasia is a distinct clinical entity, it can also occur as a feature of overgrowth syndromes, including Beckwith-Wiedemann syndrome (BWS; 130650), neurofibromatosis (NF1; 162200), Proteus syndrome (176920), and Klippel-Trenaunay-Weber syndrome (149000) (Shuman et al., 2006).
Deafness enamel hypoplasia nail defects
MedGen UID:
343498
Concept ID:
C1856186
Disease or Syndrome
Hall Riggs mental retardation syndrome
MedGen UID:
341089
Concept ID:
C1856198
Disease or Syndrome
Hair defect with photosensitivity and mental retardation
MedGen UID:
383868
Concept ID:
C1856241
Disease or Syndrome
Growth retardation, small and puffy hands and feet, and eczema
MedGen UID:
343510
Concept ID:
C1856242
Disease or Syndrome
Gonadal dysgenesis, xy type, with associated anomalies
MedGen UID:
344696
Concept ID:
C1856272
Disease or Syndrome
Ermine phenotype
MedGen UID:
346466
Concept ID:
C1856899
Disease or Syndrome
Epilepsy telangiectasia
MedGen UID:
384017
Concept ID:
C1856929
Disease or Syndrome
Epilepsy occipital calcifications
MedGen UID:
341654
Concept ID:
C1856930
Disease or Syndrome
Encephalopathy with intracranial calcification, growth hormone deficiency, microcephaly, and retinal degeneration
MedGen UID:
346482
Concept ID:
C1856973
Disease or Syndrome
Ectodermal dysplasia, hypohidrotic, with hypothyroidism and agenesis of the corpus callosum
MedGen UID:
347363
Concept ID:
C1857053
Disease or Syndrome
Ectodermal dysplasia and neurosensory deafness
MedGen UID:
346503
Concept ID:
C1857068
Disease or Syndrome
DK phocomelia syndrome
MedGen UID:
341728
Concept ID:
C1857226
Disease or Syndrome
Trichohepatoenteric syndrome
MedGen UID:
347405
Concept ID:
C1857276
Disease or Syndrome
Although the spectrum of phenotypic expression in trichohepatoenteric syndrome (THES) is broad, the characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients (summary by Fabre et al., 2007). Genetic Heterogeneity of Trichohepatoenteric Syndrome Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by mutation in the SKIV2L gene (600478) on chromosome 6p21.3.
Donnai Barrow syndrome
MedGen UID:
347406
Concept ID:
C1857277
Disease or Syndrome
Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (ocular hypertelorism, enlarged fontanelle), ocular findings (high myopia, retinal detachment, progressive vision loss, and iris coloboma), sensorineural hearing loss, agenesis of the corpus callosum, intellectual disability, and congenital diaphragmatic hernia (CDH) and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed.
Diabetes insipidus, nephrogenic, with mental retardation and intracerebral calcification
MedGen UID:
387791
Concept ID:
C1857297
Disease or Syndrome
Dermatoleukodystrophy
MedGen UID:
387794
Concept ID:
C1857314
Disease or Syndrome
Deafness, conductive, with malformed external ear
MedGen UID:
347429
Concept ID:
C1857341
Disease or Syndrome
Dandy-Walker malformation with mental retardation, macrocephaly, myopia and brachytelephalangy
MedGen UID:
341752
Concept ID:
C1857352
Disease or Syndrome
Craniotelencephalic dysplasia
MedGen UID:
347462
Concept ID:
C1857471
Disease or Syndrome
Cardiocranial syndrome
MedGen UID:
346598
Concept ID:
C1857495
Disease or Syndrome
Multiple cardiocranial defects, including craniosynostosis, cardiovascular malformations, mandibular ankylosis, and other dysmorphic features occurring in various associations.
Craniofacial dyssynostosis
MedGen UID:
347473
Concept ID:
C1857511
Disease or Syndrome
Temtamy syndrome
MedGen UID:
347474
Concept ID:
C1857512
Disease or Syndrome
Temtamy syndrome is a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus (summary by Akizu et al., 2013).
Cortical blindness, retardation, and postaxial polydactyly
MedGen UID:
347487
Concept ID:
C1857568
Disease or Syndrome
COACH syndrome
MedGen UID:
387879
Concept ID:
C1857662
Disease or Syndrome
COACH syndrome is an autosomal recessive disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Other features, such as coloboma and renal cysts, may be variable. COACH syndrome is considered by some to be a subtype of Joubert syndrome (JBTS; 213300) with congenital hepatic fibrosis. Identification of liver disease in these patients is critical because some may develop complications such as portal hypertension with fatal variceal bleeding (Brancati et al., 2008; Doherty et al., 2010).
Yunis Varon syndrome
MedGen UID:
341818
Concept ID:
C1857663
Disease or Syndrome
Yunis-Varon syndrome is a severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. The disorder is usually lethal in infancy (summary by Campeau et al., 2013).
Microhydranencephaly
MedGen UID:
341899
Concept ID:
C1857977
Disease or Syndrome
Microhydranencephaly (MHAC) is a severe neurodevelopmental defect characterized by extreme microcephaly, profound motor and mental retardation, spasticity, and incomplete cerebral formation. Radiologic studies show gross dilation of the ventricles resulting from the absence of cerebral hemispheres or severe delay in their development, as well as hypoplasia of the corpus callosum, cerebellum, and brainstem (summary by Guven et al., 2012).
Hydronephrosis, congenital, with cleft palate, characteristic facies, hypotonia, and mental retardation
MedGen UID:
387971
Concept ID:
C1858043
Disease or Syndrome
Congenital Cataracts, Facial Dysmorphism, and Neuropathy
MedGen UID:
346973
Concept ID:
C1858726
Congenital Abnormality
Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is characterized by abnormalities of the eye (bilateral congenital cataracts, microcornea, microphthalmia, micropupils); mildly dysmorphic facial features apparent in late childhood; and a hypo/demyelinating, symmetric, distal peripheral neuropathy. The neuropathy is predominantly motor at the onset and results in delays in early motor development, progressing to severe disability by the third decade. Secondary scoliosis and foot deformities are common. Sensory neuropathy develops after age ten years. Most affected individuals have a mild non-progressive intellectual deficit and cerebellar involvement including ataxia, nystagmus, intention tremor, and dysmetria. All have short stature and subnormal weight. Adults have hypogonadotropic hypogonadism. Parainfectious rhabdomyolysis (profound muscle weakness, myoglobinuria, and excessively elevated serum concentration of creatine kinase usually following a viral infection) is a potentially life-threatening complication. To date all affected individuals and carriers identified have been from the Roma/Gypsy population.
Congenital central hypoventilation
MedGen UID:
347052
Concept ID:
C1859049
Disease or Syndrome
Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory and autonomic regulation. It is typically characterized by a classic presentation in newborns and, rarely, a milder later-onset (LO-CCHS) presentation in toddlers, children, and adults. Classic CCHS presents in newborns as: Apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; Autonomic nervous system dysregulation (ANSD); and In some individuals, altered development of neural crest-derived structures (i.e., Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Individuals with CCHS who have been diagnosed as newborns and ventilated conservatively and consistently throughout childhood have now reached the age of 20 to 30 years; they are highly functional and live independently. LO-CCHS manifests as nocturnal alveolar hypoventilation and mild ANSD. Individuals with LO-CCHS who were not identified until age 20 years or older have now reached the age of 30 to 55 years.
Choroid plexus calcification with mental retardation
MedGen UID:
395174
Concept ID:
C1859092
Disease or Syndrome
Griscelli syndrome type 1
MedGen UID:
347092
Concept ID:
C1859194
Disease or Syndrome
Griscelli syndrome type 1 (GS1) represents hypomelanosis with a primary neurologic deficit and without immunologic impairment or manifestations of hemophagocytic syndrome (Menasche et al., 2002). Griscelli syndrome with immune impairment, or Griscelli syndrome type 2 (607624), is caused by mutation in the RAB27A gene (603868). Griscelli syndrome type 3 (609227), characterized by hypomelanosis with no immunologic or neurologic manifestations, can be caused by mutation in the melanophilin (MLPH; 606526) or MYO5A genes. Griscelli syndrome is a rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. While most patients also develop hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation (Menasche et al., 2000), some show severe neurologic impairment early in life without apparent immune abnormalities. Bahadoran et al. (2003) characterized GS1 as comprising hypomelanosis and severe central nervous system dysfunction, corresponding to the 'dilute' phenotype in the mouse, and GS2 as comprising hypomelanosis and lymphohistiocytotic hemophagocytosis, corresponding to the 'ashen' phenotype in mouse. Anikster et al. (2002), Menasche et al. (2002), Huizing et al. (2002), and Bahadoran et al. (2003, 2003) suggested that Elejalde syndrome (256710) in some patients and GS1 represent the same entity.
Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome
MedGen UID:
347111
Concept ID:
C1859252
Disease or Syndrome
Spinocerebellar ataxia, autosomal recessive 2
MedGen UID:
349134
Concept ID:
C1859298
Disease or Syndrome
Cerebellar vermis aplasia with associated features suggesting Smith-Lemli-Opitz syndrome and Meckel syndrome
MedGen UID:
347120
Concept ID:
C1859300
Disease or Syndrome
Camptodactyly, fibrous tissue hyperplasia, and skeletal dysplasia
MedGen UID:
395240
Concept ID:
C1859357
Disease or Syndrome
Camptodactyly syndrome Guadalajara type 1
MedGen UID:
395241
Concept ID:
C1859359
Disease or Syndrome
Brachymetapody-anodontia-hypotrichosis-albinoidism
MedGen UID:
347867
Concept ID:
C1859385
Disease or Syndrome
Bowen-Conradi syndrome
MedGen UID:
349160
Concept ID:
C1859405
Disease or Syndrome
Bowen-Conradi syndrome is a disorder that affects many parts of the body and is usually fatal in infancy. Affected individuals have a low birth weight, experience feeding problems, and grow very slowly. Their head is unusually small overall (microcephaly), but is longer than expected compared with its width (dolicocephaly). Characteristic facial features include a prominent, high-bridged nose and an unusually small jaw (micrognathia) and chin. Affected individuals typically have pinky fingers that are curved toward or away from the ring finger (fifth finger clinodactyly) or permanently flexed (camptodactyly), feet with soles that are rounded outward (rocker-bottom feet), and restricted joint movement. Other features that occur in some affected individuals include seizures; structural abnormalities of the kidneys, heart, brain, or other organs; and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Affected males may have the opening of the urethra on the underside of the penis (hypospadias) or undescended testes (cryptorchidism). Babies with Bowen-Conradi syndrome do not achieve developmental milestones such as smiling or sitting, and they usually do not survive more than 6 months.
Blepharophimosis with ptosis, syndactyly, and short stature
MedGen UID:
347880
Concept ID:
C1859432
Disease or Syndrome
Microcephalic osteodysplastic primordial dwarfism type 2
MedGen UID:
347148
Concept ID:
C1859451
Disease or Syndrome
Microcephalic osteodysplastic primordial dwarfism type II is characterized by intrauterine growth retardation, severe proportionate short stature, and microcephaly. It is distinct from Seckel syndrome (see 210600) by more severe growth retardation, radiologic abnormalities, and absent or mild mental retardation (summary by Willems et al., 2010).
Bird headed dwarfism Montreal type
MedGen UID:
347890
Concept ID:
C1859468
Disease or Syndrome
Bardet-Biedl syndrome 8
MedGen UID:
347181
Concept ID:
C1859566
Disease or Syndrome
Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.
Bardet-Biedl syndrome 10
MedGen UID:
347909
Concept ID:
C1859568
Disease or Syndrome
Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.
Bardet-Biedl syndrome 12
MedGen UID:
347910
Concept ID:
C1859570
Disease or Syndrome
Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.
Aural atresia, multiple congenital anomalies, and mental retardation
MedGen UID:
347912
Concept ID:
C1859591
Disease or Syndrome
Adult onset ataxia with oculomotor apraxia
MedGen UID:
395301
Concept ID:
C1859598
Disease or Syndrome
Ataxia with oculomotor apraxia type 1 (AOA1) is characterized by childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. The first manifestation is progressive gait imbalance (mean age of onset: 4.3 years; range: 2-10 years), followed by dysarthria, then upper-limb dysmetria with mild intention tremor. Oculomotor apraxia, usually noticed a few years after the onset of ataxia, progresses to external ophthalmoplegia. All affected individuals have generalized areflexia followed by a peripheral neuropathy and quadriplegia with loss of ambulation about seven to ten years after onset. Hands and feet are short and atrophic. Chorea and upper-limb dystonia are common. Intellect remains normal in some individuals; in others, different degrees of cognitive impairment have been observed.
Illum syndrome
MedGen UID:
349231
Concept ID:
C1859711
Disease or Syndrome
Arterial tortuosity syndrome
MedGen UID:
347942
Concept ID:
C1859726
Disease or Syndrome
Arterial tortuosity syndrome (ATS) is characterized by: Severe and widespread arterial tortuosity of the aorta and middle-sized arteries (with an increased risk of aneurysms and dissections) and focal and widespread stenosis which can involve the aorta and/or pulmonary arteries; ??The risk for ischemic vascular events involving cerebrovascular circulation and the abdominal arteries is increased. In addition, large veins may be dilated and valvular regurgitation and mitral valve prolapse can occur. Craniofacial involvement with characteristic facies and high palate with dental crowding; Soft/doughy skin and other evidence of a generalized connective tissue disorder including skeletal findings (scoliosis, pectus excavatum/carinatum, joint laxity, knee/elbow contractures, arachnodactyly, camptodactyly); inguinal/abdominal wall hernia; sliding hiatal or diaphragmatic hernia; hypotonia; and ocular involvement (myopia, keratoconus).
Microphthalmia syndromic 3
MedGen UID:
347232
Concept ID:
C1859773
Disease or Syndrome
SOX2-related eye disorders are characterized by anophthalmia and/or microphthalmia that is usually bilateral, severe, and apparent at birth or by prenatal ultrasound examination. Other common findings include brain malformations, esophageal atresia, cryptorchidism and/or micropenis in males, and hypogonadotropic hypogonadism and/or pituitary hypoplasia. Postnatal growth failure, delayed motor development, and learning disability are common.
Aniridia renal agenesis psychomotor retardation
MedGen UID:
347952
Concept ID:
C1859782
Disease or Syndrome
Microcephaly albinism digital anomalies syndrome
MedGen UID:
395372
Concept ID:
C1859910
Disease or Syndrome
Alaninuria with microcephaly, dwarfism, enamel hypoplasia and diabetes mellitus
MedGen UID:
348505
Concept ID:
C1859965
Disease or Syndrome
Acrofrontofacionasal dysostosis syndrome
MedGen UID:
349729
Concept ID:
C1860118
Disease or Syndrome
Achondroplasia and severe combined immunodeficiency
MedGen UID:
348040
Concept ID:
C1860168
Disease or Syndrome
Achalasia microcephaly syndrome
MedGen UID:
349753
Concept ID:
C1860212
Disease or Syndrome
Ablepharon macrostomia syndrome
MedGen UID:
395439
Concept ID:
C1860224
Disease or Syndrome
Stoll Alembik Dott syndrome
MedGen UID:
395493
Concept ID:
C1860471
Disease or Syndrome
Say Field Coldwell syndrome
MedGen UID:
348711
Concept ID:
C1860805
Disease or Syndrome
Thumb stiff brachydactyly mental retardation
MedGen UID:
396073
Concept ID:
C1861166
Disease or Syndrome
Thumb deformity and alopecia
MedGen UID:
348284
Concept ID:
C1861168
Disease or Syndrome
Paris-Trousseau thrombocytopenia
MedGen UID:
349973
Concept ID:
C1861178
Disease or Syndrome
Stratton-Parker syndrome
MedGen UID:
350025
Concept ID:
C1861448
Disease or Syndrome
BOD syndrome
MedGen UID:
350585
Concept ID:
C1862082
Disease or Syndrome
Brachydactyly-nystagmus-cerebellar ataxia
MedGen UID:
350589
Concept ID:
C1862099
Disease or Syndrome
Bowing of legs, anterior with dwarfism
MedGen UID:
350610
Concept ID:
C1862172
Disease or Syndrome
The diagnostic hallmarks of Weismann-Netter syndrome (WNS) are anterior bowing of the diaphyses of the tibia and fibula, broadening or 'tibialization' of the fibula, posterior cortical thickening of both bones, and short stature. The diaphyses of other long bones may be similarly affected, but usually to a milder degree. Some WNS patients have also displayed mental retardation (summary by Peippo et al., 2009).
Aortic arch anomaly with peculiar facies and mental retardation
MedGen UID:
350734
Concept ID:
C1862682
Disease or Syndrome
AGLOSSIA-ADACTYLIA
MedGen UID:
354928
Concept ID:
C1863203
Disease or Syndrome
Acropectorovertebral dysplasia F form
MedGen UID:
400262
Concept ID:
C1863307
Disease or Syndrome
Acropectorovertebral dysgenesis, or F syndrome, is an autosomal dominant skeletal dysplasia characterized by carpal and tarsal synostoses, syndactyly between the first and second fingers, hypodactyly and polydactyly of feet, and abnormalities of the sternum and spine (summary by Thiele et al., 2004).
Young Simpson syndrome
MedGen UID:
350209
Concept ID:
C1863557
Disease or Syndrome
Say-Barber-Biesecker-Young-Simpson syndrome, a variant of Ohdo syndrome (249620), is characterized by distinctive facial appearance with severe blepharophimosis, an immobile mask-like face, a bulbous nasal tip, and a small mouth with a thin upper lip. The condition presents in infancy with severe hypotonia and feeding problems. Associated skeletal problems include joint laxity, abnormally long thumbs and great toes, and dislocated or hypoplastic patellae. Structural cardiac defects are present in around 50% of cases, and dental anomalies, including small and pointed teeth, are common. Many affected individuals have abnormalities of thyroid structure or function. YSS is usually associated with severe mental retardation, delayed motor milestones, and significantly impaired speech (summary by Clayton-Smith et al., 2011). Genitopatellar syndrome (606170) is an allelic disorder with overlapping features.
Spondyloepimetaphyseal dysplasia with multiple dislocations
MedGen UID:
350960
Concept ID:
C1863732
Disease or Syndrome
Spondyloepimetaphyseal dysplasia with joint laxity type 2 (SEMDJL2) is characterized by short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalized ligamentous laxity, and mild spinal deformity. Intellectual development is not impaired. Radiographic characteristics include significantly retarded epiphyseal ossification that evolves into epiphyseal dysplasia and precocious osteoarthritis, metaphyseal irregularities and vertical striations, constricted femoral neck, slender metacarpals and metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or mild platyspondyly (summary by Min et al., 2011). The most distinctive features for differential diagnosis of SEMDJL2 are the slender metacarpals and phalanges and the progressive degeneration of carpal bones; however, these 2 features are evident only in older children and young adults. The soft consistency of cartilage in the airways leads to laryngotracheomalacia with proneness to respiratory obstruction and inspiratory stridor in infancy and childhood (summary by Boyden et al., 2011).
HYPOSPADIAS, HYPERTELORISM, UPPER LID COLOBOMA, AND MIXED-TYPE HEARING LOSS
MedGen UID:
400396
Concept ID:
C1863870
Disease or Syndrome
Radioulnar synostosis with microcephaly, short stature, scoliosis, and mental retardation
MedGen UID:
400399
Concept ID:
C1863881
Disease or Syndrome
Congenital disorder of glycosylation type 1C
MedGen UID:
400469
Concept ID:
C1864178
Disease or Syndrome
Congenital disorders of N-linked glycosylation (abbreviated here as CDG-N-linked), are a group of disorders of N-linked oligosaccharides caused by deficiency in 42 different enzymes in the N-linked synthetic pathway. Most commonly, the disorders begin in infancy; manifestations range from severe developmental delay and hypotonia with multiple organ system involvement to hypoglycemia and protein-losing enteropathy with normal development. However, most types have been described in only a few individuals, and thus understanding of the phenotypes is limited. In PMM2-CDG (CDG-Ia), the most common type reported, the clinical presentation and course are highly variable, ranging from death in infancy to mild involvement in adults.
Craniosynostosis, anal anomalies, and porokeratosis
MedGen UID:
351066
Concept ID:
C1864186
Disease or Syndrome
Muenke syndrome
MedGen UID:
355217
Concept ID:
C1864436
Congenital Abnormality
Muenke syndrome is defined by the presence of the specific FGFR3 pathogenic variant, c.749C>G, that results in the protein change p.Pro250Arg. Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pan synostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (reduced anteroposterior dimenstion of the skull), although turribrachycephaly (a "tower-shaped" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: temporal bossing; widely spaced eyes, ptosis or proptosis (usually mild); midface retrusion; and highly arched palate or cleft lip and palate. Strabismus is common. Other findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); epilepsy; intracranial anomalies; intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family. Of note, some individuals who have the p.Pro250Arg pathogenic variant may have no signs of Muenke syndrome on physical or radiographic examination.
Growth and mental retardation, mandibulofacial dysostosis, microcephaly, and cleft palate
MedGen UID:
355264
Concept ID:
C1864652
Disease or Syndrome
Mandibulofacial dysostosis with microcephaly (MFDM) is characterized by malar and mandibular hypoplasia; microcephaly (congenital or postnatal onset); malformations of the pinna, auditory canal, and/or middle ear (ossicles and semi-circular canals) with associated conductive hearing loss; and distinctive facial features (metopic ridge, up- or downslanting palpebral fissures, prominent glabella, broad nasal bridge, bulbous nasal tip, and everted lower lip). Associated craniofacial malformations may include cleft palate, choanal atresia, and facial asymmetry. Intellectual disability is a prominent feature. Major extracranial malformations include: esophageal atresia (~40%), congenital heart disease (~40%), and thumb abnormalities (~25%). Short stature is present in approximately one third of individuals.
Microphthalmia syndromic 6
MedGen UID:
355268
Concept ID:
C1864689
Disease or Syndrome
Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). Microphthalmia is defined as a globe with a total axial length (TAL) that is at least two standard deviations below the mean for age. Classification of microphthalmia is according to the anatomic appearance of the globe and severity of axial length reduction. Severe microphthalmia refers to a globe with a corneal diameter less than 4 mm and a TAL less than 10 mm at birth or less than 12 mm after age one year. Simple microphthalmia refers to an eye that is anatomically intact except for its short TAL. Complex microphthalmia refers to an eye with anterior segment dysgenesis and/or posterior segment dysgenesis. Anophthalmia/microphthalmia (A/M) can be unilateral or bilateral. A/M is a heterogenous condition with various etiologies. It can be isolated or can occur with other anomalies or as part of a well-defined syndrome. One-third of individuals with A/M have associated malformations. Heritable causes of A/M include chromosome abnormalities and syndromic or nonsyndromic single gene disorders.
Frias syndrome
MedGen UID:
400621
Concept ID:
C1864825
Disease or Syndrome
Frias syndrome is characterized by mild exophthalmia, palpebral ptosis, hypertelorism, short square hands with minimal proximal syndactyly between the second and third fingers, small broad great toes, and short stature. Some patients may exhibit bilateral pedunculated postminimi (summary by Martinez-Fernandez et al., 2014).
Combined oxidative phosphorylation deficiency 3
MedGen UID:
355842
Concept ID:
C1864840
Disease or Syndrome
Koolen-de Vries syndrome
MedGen UID:
355853
Concept ID:
C1864871
Disease or Syndrome
The KANSL1-related intellectual disability syndrome is characterized by developmental delay/intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Global psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with the KANSL1-related intellectual disability syndrome function in the mild to moderate range of intellectual disability. Other findings include epilepsy (55%), congenital heart defects (39%), renal and urologic anomalies (37%), and cryptorchidism (71% of males). Behavior in most is described as friendly, amiable, and cooperative.
Scaphocephaly, maxillary retrusion, and mental retardation
MedGen UID:
355365
Concept ID:
C1865070
Disease or Syndrome
Anal atresia, hypospadias, and penoscrotal inversion
MedGen UID:
355405
Concept ID:
C1865208
Disease or Syndrome
Arterial occlusive disease, progressive, with hypertension, heart defects, bone fragility, and brachysyndactyly
MedGen UID:
355427
Concept ID:
C1865267
Disease or Syndrome
Megalencephaly cutis marmorata telangiectatica congenita
MedGen UID:
355421
Concept ID:
C1865285
Disease or Syndrome
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria (summary by Mirzaa et al., 2012). This disorder is also known as the macrocephaly-capillary malformation (MCM) syndrome (Conway et al., 2007). Mirzaa et al. (2012) suggested use of the term MCAP rather than MCM to reflect the very large brain size, rather than simply large head size, that characterizes this syndrome, and the importance and high frequency of perisylvian polymicrogyria.
Desmosterolosis
MedGen UID:
400801
Concept ID:
C1865596
Disease or Syndrome
Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells (summary by Waterham et al., 2001).
Patterson Stevenson syndrome
MedGen UID:
357124
Concept ID:
C1866741
Disease or Syndrome
Splenogonadal fusion limb defects micrognatia
MedGen UID:
401073
Concept ID:
C1866745
Disease or Syndrome
Splenogonadal fusion (SGF) is a rare congenital anomaly of abnormal fusion between the spleen and the gonad or the remnants of the mesonephros. In 'continuous SGF,' there is a cord-like connection between the 2 organs, whereas in 'discontinuous SGF,' there is fusion of accessory splenic tissue and the gonad without a distinct structural connection to the spleen itself. Forty-eight percent of individuals with continuous SGF have additional malformations, compared to 9% of those with discontinuous SGF (McPherson et al., 2003).
Speech development, delayed, with facial asymmetry, strabismus, and transverse earlobe crease
MedGen UID:
355803
Concept ID:
C1866802
Disease or Syndrome
Spastic paraplegia with precocious puberty
MedGen UID:
401096
Concept ID:
C1866850
Disease or Syndrome
Spastic paraplegia, sensorineural deafness, mental retardation, and progressive nephropathy
MedGen UID:
355816
Concept ID:
C1866853
Disease or Syndrome
Shprintzen omphalocele syndrome
MedGen UID:
356653
Concept ID:
C1866958
Disease or Syndrome
Scholte syndrome
MedGen UID:
401129
Concept ID:
C1866985
Disease or Syndrome
Say syndrome
MedGen UID:
357895
Concept ID:
C1867023
Disease or Syndrome
Pterygia, mental retardation and distinctive craniofacial features
MedGen UID:
357988
Concept ID:
C1867443
Disease or Syndrome
Telfer Sugar Jaeger syndrome
MedGen UID:
358177
Concept ID:
C1868311
Disease or Syndrome
Pelvis-shoulder dysplasia
MedGen UID:
356991
Concept ID:
C1868508
Disease or Syndrome
Leukodystrophy, adult-onset, autosomal dominant
MedGen UID:
356995
Concept ID:
C1868512
Disease or Syndrome
Autosomal dominant adult-onset demyelinating leukodystrophy is a slowly progressive and fatal disorder that presents in the fourth or fifth decade of life and is characterized clinically by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. ADLD differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis (summary by Padiath et al., 2006). Characteristic MRI findings include T2-weighted hyperintense changes in the upper corticospinal tract and cerebellar peduncles, with later development of confluent white matter changes in the frontoparietal area with relative sparing of the periventricular white matter (summary by Schuster et al., 2011).
Patterson pseudoleprechaunism syndrome
MedGen UID:
358350
Concept ID:
C1868546
Disease or Syndrome
Char syndrome
MedGen UID:
358356
Concept ID:
C1868570
Disease or Syndrome
Char syndrome is characterized by the triad of typical facial features, patent ductus arteriosus (PDA), and aplasia or hypoplasia of the middle phalanges of the fifth fingers. Typical facial features are flat midface, flat nasal bridge and broad flat nasal tip, wide-set eyes, downslanting palpebral fissures, mild ptosis, short philtrum resulting in a triangular mouth, and thickened (patulous) everted lips.
Thanatophoric dysplasia type 1
MedGen UID:
358383
Concept ID:
C1868678
Congenital Abnormality
Thanatophoric dysplasia (TD) is a short-limb dwarfism syndrome that is usually lethal in the perinatal period. TD is divided into type I, characterized by micromelia with bowed femurs and, uncommonly, the presence of cloverleaf skull deformity (Kleeblattschädel) of varying severity; and type II, characterized by micromelia with straight femurs and uniform presence of moderate-to-severe cloverleaf skull deformity. Other features common to type I and type II include: short ribs, narrow thorax, macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Rare long-term survivors have been reported.
4p partial monosomy syndrome
MedGen UID:
408255
Concept ID:
C1956097
Disease or Syndrome
Wolf-Hirschhorn syndrome (WHS) is characterized by typical craniofacial features in infancy consisting of 'Greek warrior helmet appearance' of the nose (the broad bridge of the nose continuing to the forehead), microcephaly, high forehead with prominent glabella, ocular hypertelorism, epicanthus, highly arched eyebrows, short philtrum, downturned mouth, micrognathia, and poorly formed ears with pits/tags. All affected individuals have prenatal-onset growth deficiency followed by postnatal growth retardation and hypotonia with muscle underdevelopment. Developmental delay/intellectual disability of variable degree is present in all. Seizures occur in 50% to 100% of children with WHS. Other findings include skeletal anomalies (60%-70%), congenital heart defects (~50%), hearing loss (mostly conductive) (>40%), urinary tract malformations (25%), and structural brain abnormalities (33%).
Mevalonic aciduria
MedGen UID:
368373
Concept ID:
C1959626
Disease or Syndrome
Mevalonic aciduria, the first recognized defect in the biosynthesis of cholesterol and isoprenoids, is a consequence of a deficiency of mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36). Mevalonic acid accumulates because of failure of conversion to 5-phosphomevalonic acid, which is catalyzed by mevalonate kinase. Mevalonic acid is synthesized from 3-hydroxy-3-methylglutaryl-CoA, a reaction catalyzed by HMG-CoA reductase (142910). Mevalonic aciduria is characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and to periodic fever syndrome (HIDS; 260920), which is also caused by mutation in the MVK gene (summary by Prietsch et al, 2003).
Mental retardation, X-linked, syndromic 13
MedGen UID:
368466
Concept ID:
C1968550
Disease or Syndrome
The MECP2 gene is mutated in Rett syndrome (RTT; 312750), a severe neurodevelopmental disorder that almost always occurs in females. Males with non-RTT mutations in the MECP2 gene can demonstrate a wide variety of phenotypes, including X-linked mental retardation with spasticity and other variable features, described here, and Lubs X-linked mental retardation syndrome (MRXSL; 300260). Males with RTT-associated MECP2 mutations have neonatal severe encephalopathy that is usually lethal (300673) (Moog et al., 2003; Villard, 2007).
Mental retardation, autosomal dominant 1
MedGen UID:
409857
Concept ID:
C1969562
Disease or Syndrome
Ataxia, spastic, 3, autosomal recessive
MedGen UID:
370715
Concept ID:
C1969645
Disease or Syndrome
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation
MedGen UID:
370845
Concept ID:
C1970180
Disease or Syndrome
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is characterized by slowly progressive cerebellar ataxia and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. The neurologic dysfunction involves the legs more than the arms. The tendon reflexes are retained. Deterioration of motor skills usually starts in childhood or adolescence, but occasionally not until adulthood. Dysarthria develops over time. Occasional findings include: epilepsy; learning problems; cognitive decline; and reduced consciousness, neurologic deterioration, and fever following minor head trauma. Many affected individuals become wheelchair dependent in their teens or twenties. Neonatal or early-infantile onset patients have a severe disease course and may die, whereas late-infantile and early-childhood onset is associated with early wheelchair dependency.
Pitt-Hopkins syndrome
MedGen UID:
370910
Concept ID:
C1970431
Disease or Syndrome
Pitt-Hopkins syndrome (PTHS) is characterized by distinctive facial features which become more apparent with age (100%), developmental delay/intellectual disability (100%), and episodic hyperventilation and/or breath-holding while awake (55%-60%). Global developmental delays are significant and intellectual disability is moderate to severe: mean age of walking is four to six years; most affected individuals are nonverbal. Other common findings are behavioral issues, hand stereotypic movements, seizures (40%-50%), constipation, and severe myopia.
Potocki-Lupski syndrome
MedGen UID:
410082
Concept ID:
C1970482
Disease or Syndrome
Potocki-Lupski syndrome is a developmental disorder characterized by hypotonia, failure to thrive, mental retardation, pervasive developmental disorders, and congenital anomalies. All reported cases have occurred sporadically without bias in the parental origin of rearrangements. Most duplications are 3.7 Mb in size and only identifiable by array comparative genomic hybridization (CGH) analysis. Approximately 60% of PTLS patients harbor a microduplication of chromosome 17p11.2 reciprocal to the common recurrent 3.7-Mb microdeletion in SMS (summary by Shchelochkov et al., 2010).
Phosphoribosylpyrophosphate synthetase superactivity
MedGen UID:
370358
Concept ID:
C1970827
Disease or Syndrome
Phosphoribosylpyrophosphate synthetase (PRS) superactivity is characterized by hyperuricemia and hyperuricosuria and is divided into a severe phenotype with infantile or early-childhood onset and a milder phenotype with late-juvenile or early-adult onset. Variable combinations of sensorineural hearing loss, hypotonia, and ataxia observed in the severe type are not usually present in the mild type. In the mild type, uric acid crystalluria or a urinary stone is commonly the first clinical finding, followed later by gouty arthritis if serum urate concentration is not controlled.
I cell disease
MedGen UID:
435914
Concept ID:
C2673377
Disease or Syndrome
Mucolipidosis II (ML II, I-cell disease) is a slowly progressive inborn error of metabolism with clinical onset at birth and fatal outcome most often in early childhood. Postnatal growth is limited and often ceases in the second year of life; contractures develop in all large joints. The skin is thickened, facial features are coarse, and gingiva are hypertrophic. Orthopedic abnormalities present at birth may include thoracic deformity, kyphosis, clubfeet, deformed long bones, and/or dislocation of the hip(s). Already in infancy skeletal radiographs reveal dysostosis multiplex. All children appear to have cardiac involvement, most commonly thickening and insufficiency of the mitral valve and, less frequently, the aortic valve. Progressive mucosal thickening narrows the airways and gradual stiffening of the thoracic cage contributes to respiratory insufficiency, the most common cause of death.
Hypomyelination and Congenital Cataract
MedGen UID:
382379
Concept ID:
C2674508
Disease or Syndrome
Hypomyelination and congenital cataract (HCC) is usually characterized by bilateral congenital cataracts and normal psychomotor development in the first year of life, followed by slowly progressive neurologic impairment manifest as ataxia, spasticity (brisk tendon reflexes and bilateral extensor plantar responses), and mild to moderate cognitive impairment. Dysarthria and truncal hypotonia are observed. Cerebellar signs (truncal titubation and intention tremor) and peripheral neuropathy (muscle weakness and wasting of the legs) are present in the majority of affected individuals. Seizures can occur. In a few cases cataracts may be absent.
3q29 microdeletion syndrome
MedGen UID:
393265
Concept ID:
C2674949
Disease or Syndrome
Chromosome 15q11-q13 duplication syndrome
MedGen UID:
390767
Concept ID:
C2675336
Disease or Syndrome
The features of the chromosome 15q11-q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delays, and behavioral problems (Bundey et al., 1994; Burnside et al., 2011). See also chromosome 15q13.3 deletion syndrome (612001) and chromosome 15q11.2 deletion syndrome (615656). For a discussion of genetic heterogeneity of autism, see 209850.
22q11.2 duplication syndrome
MedGen UID:
436417
Concept ID:
C2675369
Disease or Syndrome
22q11.2 duplication is defined for this GeneReview as the presence of a common 3-Mb or 1.5-Mb proximal tandem duplication. The 22q11.2 duplication phenotype appears to be generally mild and highly variable; findings range from apparently normal to intellectual disability/learning disability, delayed psychomotor development, growth retardation, and/or hypotonia. The high frequency with which the 22q11.2 duplication is found in an apparently normal parent of a proband suggests that many individuals can harbor a duplication of 22q11.2 with no discernible phenotypic effect.
Chromosome 6pter-p24 deletion syndrome
MedGen UID:
393396
Concept ID:
C2675486
Disease or Syndrome
2p15-16.1 microdeletion syndrome
MedGen UID:
390902
Concept ID:
C2675875
Disease or Syndrome
Chromosome 1q21.1 duplication syndrome
MedGen UID:
382715
Concept ID:
C2675891
Disease or Syndrome
1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1. Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. Expressive language skills (vocabulary and the production of speech) tend to be more impaired than receptive language skills (the ability to understand speech) in affected individuals. In childhood, 1q21.1 microduplications may also be associated with an increased risk of attention deficit hyperactivity disorder and other behavioral problems. Psychiatric disorders such as schizophrenia or mood disorders such as anxiety or depression occur in some affected individuals, usually during adulthood. Rarely, recurrent seizures (epilepsy) occur in people with a 1q21.1 microduplication. Some individuals with a 1q21.1 microduplication are born with malformations of the heart, including a particular combination of heart defects known as tetralogy of Fallot. Less commonly, other physical malformations such as the urethra opening on the underside of the penis (hypospadias) in males, inward- and upward-turning feet (clubfeet), or misalignment of the hip joint (hip dysplasia) are present at birth. Individuals with a 1q21.1 microduplication may also have a larger than average head size or taller than average adult stature. Some have slightly unusual facial features such as wide-set eyes or low-set ears. As adults, individuals with a 1q21.1 microduplication may be prone to develop cysts, swollen and knotted (varicose) veins, or carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. However, there is no particular pattern of physical abnormalities that characterizes 1q21.1 microduplications. Signs and symptoms related to the chromosomal change vary even among affected members of the same family. Some people with the duplication have no identified physical, intellectual, or behavioral abnormalities.
1q21.1 recurrent microdeletion
MedGen UID:
393913
Concept ID:
C2675897
Disease or Syndrome
The 1q21.1 microdeletion itself does not appear to lead to a clinically recognizable syndrome as some persons with the deletion have no obvious clinical findings and others have variable findings that most commonly include microcephaly (50%); mild intellectual disability (30%); mildly dysmorphic facial features; and eye abnormalities (26%). Other findings can include cardiac defects, genitourinary anomalies, skeletal malformations, and seizures (~15%). Psychiatric and behavioral abnormalities can include autism spectrum disorders, attention deficit hyperactivity disorder, autistic features, and sleep disturbances.
Pseudohypoparathyroidism type 1C
MedGen UID:
436554
Concept ID:
C2675910
Disease or Syndrome
Pseudohypoparathyroidism type Ic (PHP1C) is characterized by resistance to parathyroid hormone (PTH; 168450) as well as to other hormones. It is associated with a constellation of physical features referred to as Albright hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation. Laboratory studies in patients with PHP Ic show a decreased cellular cyclic AMP (cAMP) response to infused PTH, but no defect in activity of the erythrocyte Gs protein (Mantovani and Spada, 2006).
Chromosome 2q32-q33 deletion syndrome
MedGen UID:
436765
Concept ID:
C2676739
Disease or Syndrome
Glass syndrome is characterized by intellectual disability of variable severity and dysmorphic facial features, including micrognathia, downslanting palpebral fissures, cleft palate, and crowded teeth. Additional features may include seizures, joint laxity, arachnodactyly, and happy demeanor (summary by Glass et al., 1989; Urquhart et al., 2009; Rainger et al., 2014).
Dystonia 16
MedGen UID:
436979
Concept ID:
C2677567
Disease or Syndrome
15q13.3 microdeletion syndrome
MedGen UID:
393784
Concept ID:
C2677613
Disease or Syndrome
Individuals with 15q13.3 microdeletion are at increased risk for a wide range of clinical manifestations including intellectual disability, cardiac malformations, seizures, autism, and schizophrenia; however, the deletion itself does not seem to lead to a clinically recognizable syndrome and a subset of persons with the deletion have no obvious clinical findings. Behavioral problems are common and mainly comprise poor attention span, hyperactivity, mood disorder, and aggressive and/or impulsive behavior. Intellectual disability, observed in about half of the individuals with the common deletion at 15q13.3, is usually mild but can be moderate to severe.
Mental retardation and microcephaly with pontine and cerebellar hypoplasia
MedGen UID:
437070
Concept ID:
C2677903
Disease or Syndrome
Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) is an X-linked disorder affecting females and characterized by severe intellectual disability, microcephaly, and variable degrees of pontocerebellar hypoplasia. Affected individuals have very poor psychomotor development, often without independent ambulation or speech, and axial hypotonia with or without hypertonia. Some may have sensorineural hearing loss or eye anomalies. Dysmorphic features include overall poor growth, severe microcephaly (-3.5 to -10 SD), broad nasal bridge and tip, large ears, long philtrum, micrognathia, and hypertelorism (summary by Moog et al., 2011).
Mental retardation, syndromic 9, X-linked
MedGen UID:
395523
Concept ID:
C2678039
Disease or Syndrome
Christianson syndrome
MedGen UID:
394455
Concept ID:
C2678194
Disease or Syndrome
Christianson syndrome is an X-linked neurodevelopmental and progressive mental retardation syndrome characterized by microcephaly, impaired ocular movements, severe global developmental delay, developmental regression, hypotonia, abnormal movements, and early-onset seizures of variable types. Female carriers may be mildly affected (summary by Schroer et al., 2010 and Pescosolido et al., 2014).
Chromosome 22q11.2 deletion syndrome, distal
MedGen UID:
395634
Concept ID:
C2678480
Disease or Syndrome
Mental retardation with spastic paraplegia and palmoplantar hyperkeratosis
MedGen UID:
411554
Concept ID:
C2745996
Disease or Syndrome
Mental retardation with spasticity of the lower limbs (spastic paraplegia), pes cavus deformity with abnormal gait, and hyperkeratosis palmaris et plantaris.
Chromosome Xq28 duplication syndrome
MedGen UID:
411727
Concept ID:
C2749007
Disease or Syndrome
Chromosome Xp11.23-p11.22 duplication syndrome
MedGen UID:
440690
Concept ID:
C2749022
Disease or Syndrome
Atypical hemolytic-uremic syndrome 1
MedGen UID:
412743
Concept ID:
C2749604
Finding
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria)
MedGen UID:
413170
Concept ID:
C2749864
Disease or Syndrome
SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is characterized by onset of severe hypotonia in early infancy (birth to five months); severe muscular atrophy with failure to achieve independent ambulation; progressive scoliosis or kyphosis; dystonia and/or hyperkinesias (i.e., athetoid or choreiform movements); epilepsy (infantile spasms or generalized convulsions with onset from birth to three years) in a few children; postnatal growth retardation; and severe sensorineural hearing impairment. The outcome is poor with early lethality.
Chromosome 3q29 microduplication syndrome
MedGen UID:
440897
Concept ID:
C2749873
Disease or Syndrome
Chromosome 17p13.3 duplication syndrome
MedGen UID:
416374
Concept ID:
C2750748
Disease or Syndrome
Congenital muscular dystrophy, LMNA-related
MedGen UID:
413043
Concept ID:
C2750785
Disease or Syndrome
Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of inherited muscle disorders. Muscle weakness typically presents from birth to early infancy. Affected infants typically appear "floppy" with low muscle tone and poor spontaneous movements. Affected children may present with delay or arrest of gross motor development together with joint and/or spinal rigidity. Muscle weakness may improve, worsen, or stabilize in the short term; however, with time progressive weakness and joint contractures, spinal deformities, and respiratory compromise may affect quality of life and life span. The main CMD subtypes, grouped by involved protein function and gene in which causative mutations occur, are laminin alpha-2 (merosin) deficiency (MDC1A), collagen VI-deficient CMD, the dystroglycanopathies (caused by mutations in POMT1, POMT2, FKTN, FKRP, LARGE, POMGNT1, and ISPD), SEPN1-related CMD (previously known as rigid spine syndrome, RSMD1) and LMNA-related CMD (L-CMD). Several less known CMD subtypes have been reported in a limited number of individuals. Cognitive impairment ranging from intellectual disability to mild cognitive delay, structural brain and/or eye abnormalities, and seizures are found almost exclusively in the dystroglycanopathies while white matter abnormalities without major cognitive involvement tend to be seen in the laminin alpha-2-deficient subtype.
Muscular dystrophy, congenital, due to integrin alpha-7 deficiency
MedGen UID:
413044
Concept ID:
C2750786
Disease or Syndrome
Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of inherited muscle disorders. Muscle weakness typically presents from birth to early infancy. Affected infants typically appear "floppy" with low muscle tone and poor spontaneous movements. Affected children may present with delay or arrest of gross motor development together with joint and/or spinal rigidity. Muscle weakness may improve, worsen, or stabilize in the short term; however, with time progressive weakness and joint contractures, spinal deformities, and respiratory compromise may affect quality of life and life span. The main CMD subtypes, grouped by involved protein function and gene in which causative mutations occur, are laminin alpha-2 (merosin) deficiency (MDC1A), collagen VI-deficient CMD, the dystroglycanopathies (caused by mutations in POMT1, POMT2, FKTN, FKRP, LARGE, POMGNT1, and ISPD), SEPN1-related CMD (previously known as rigid spine syndrome, RSMD1) and LMNA-related CMD (L-CMD). Several less known CMD subtypes have been reported in a limited number of individuals. Cognitive impairment ranging from intellectual disability to mild cognitive delay, structural brain and/or eye abnormalities, and seizures are found almost exclusively in the dystroglycanopathies while white matter abnormalities without major cognitive involvement tend to be seen in the laminin alpha-2-deficient subtype.
Chromosome 19q13.11 deletion syndrome
MedGen UID:
414432
Concept ID:
C2751651
Disease or Syndrome
Alpha-ketoglutarate dehydrogenase deficiency
MedGen UID:
414553
Concept ID:
C2752074
Disease or Syndrome
Acromesomelic dysplasia Hunter Thompson type
MedGen UID:
419681
Concept ID:
C2930970
Disease or Syndrome
Chromosome 3pter-p25 deletion syndrome
MedGen UID:
419050
Concept ID:
C2931337
Cell or Molecular Dysfunction
Characteristic features of the distal 3p- syndrome include low birth weight, microcephaly, trigonocephaly, hypotonia, psychomotor and growth retardation, ptosis, telecanthus, downslanting palpebral fissures, and micrognathia. Postaxial polydactyly, renal anomalies, cleft palate, congenital heart defects (especially atrioventricular septal defects), preauricular pits, sacral dimple, and gastrointestinal anomalies are variable features. Although intellectual deficits are almost invariably associated with cytogenetically visible 3p deletions, rare patients with a 3p26-p25 deletion and normal intelligence or only mild abnormalities have been described (summary by Shuib et al., 2009).
Neurofibromatosis-Noonan syndrome
MedGen UID:
419089
Concept ID:
C2931482
Disease or Syndrome
Cleft lip/palate-ectodermal dysplasia syndrome
MedGen UID:
444067
Concept ID:
C2931488
Disease or Syndrome
Spinocerebellar degeneration with slow eye movements
MedGen UID:
419522
Concept ID:
C2931904
Disease or Syndrome
N syndrome
MedGen UID:
424834
Concept ID:
C2936859
Disease or Syndrome
16p11.2 deletion syndrome
MedGen UID:
461504
Concept ID:
C3150154
Disease or Syndrome
16p11.2 microdeletion is characterized by developmental delay, intellectual disability, and/or autism spectrum disorder (ASD). Developmental delays are more related to diminished language and cognitive function than motor disability. Although IQ scores range from mild intellectual disability to normal, those with IQ scores in the average range typically have other developmental issues such as language delay or ASD. Expressive language appears to be more affected than receptive language. Individuals with 16p11.2 microdeletion are at increased risk of being overweight and obese, and may be at higher than average risk for seizures and/or EEG abnormalities. As a group, they do not have a higher risk for other severe neurologic disorders, or other medical problems.
Chromosome 6q24-q25 deletion syndrome
MedGen UID:
461565
Concept ID:
C3150215
Disease or Syndrome
Homocystinuria due to CBS deficiency
MedGen UID:
461694
Concept ID:
C3150344
Disease or Syndrome
Homocystinuria caused by cystathionine ß-synthase (CBS) deficiency is characterized by developmental delay/intellectual disability, ectopia lentis and/or severe myopia, skeletal abnormalities (excessive height and length of the limbs), and thromboembolism. Expressivity is variable for all of the clinical signs. Two phenotypic variants are recognized, B6-responsive homocystinuria and B6-non-responsive homocystinuria. B6-responsive homocystinuria is typically, but not always, milder than the non-responsive variant. In the majority of untreated affected individuals, ectopia lentis occurs by age eight years. Individuals are often tall and slender with an asthenic (‘marfanoid’) habitus and are prone to osteoporosis. Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6 non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation, malar flush, livedo reticularis, and pancreatitis.
Chromosome 17q23.1-q23.2 deletion syndrome
MedGen UID:
461957
Concept ID:
C3150607
Disease or Syndrome
15q24 deletion syndrome
MedGen UID:
462024
Concept ID:
C3150674
Disease or Syndrome
The 15q24 microdeletion syndrome is characterized by global developmental delay; mild to severe (usually at least moderate) intellectual disability; facial dysmorphisms; congenital malformations of the hands and feet, eye, and genitalia; joint laxity; and growth retardation and failure to thrive. Less common findings include: seizures; conductive and sensorineural hearing loss; hypospadias and/ or micropenis. Males and females are affected equally.
Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations
MedGen UID:
462050
Concept ID:
C3150700
Disease or Syndrome
Frontonasal dysplasia 2
MedGen UID:
462053
Concept ID:
C3150703
Disease or Syndrome
Frontonasal dysplasia is a condition that results from abnormal development of the head and face before birth. People with frontonasal dysplasia have at least two of the following features: widely spaced eyes (ocular hypertelorism); a broad nose; a slit (cleft) in one or both sides of the nose; no nasal tip; a central cleft involving the nose, upper lip, or roof of the mouth (palate); incomplete formation of the front of the skull with skin covering the head where bone should be (anterior cranium bifidum occultum); or a widow's peak hairline. Other features of frontonasal dysplasia can include additional facial malformations, absence or malformation of the tissue that connects the left and right halves of the brain (the corpus callosum), and intellectual disability. There are at least three types of frontonasal dysplasia that are distinguished by their genetic causes and their signs and symptoms. In addition to the features previously described, each type of frontonasal dysplasia is associated with other distinctive features. Individuals with frontonasal dysplasia type 1 typically have abnormalities of the nose, a long area between the nose and upper lip (philtrum), and droopy upper eyelids (ptosis). Individuals with frontonasal dysplasia type 2 can have hair loss (alopecia) and an enlarged opening in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). Males with this form of the condition often have genital abnormalities. Features of frontonasal dysplasia type 3 include eyes that are missing (anophthalmia) or very small (microphthalmia) and low-set ears that are rotated backward. Frontonasal dysplasia type 3 is typically associated with the most severe facial abnormalities, but the severity of the condition varies widely, even among individuals with the same type. Life expectancy of affected individuals depends on the severity of the malformations and whether or not surgical intervention can improve associated health problems, such as breathing and feeding problems caused by the facial clefts.
Chromosome 14q11-q22 deletion syndrome
MedGen UID:
462057
Concept ID:
C3150707
Disease or Syndrome
Chromosome 4q21 deletion syndrome
MedGen UID:
462106
Concept ID:
C3150756
Disease or Syndrome
Chromosome 17q21.31 duplication syndrome
MedGen UID:
462137
Concept ID:
C3150787
Disease or Syndrome
Chromosome 16p12.2-p11.2 deletion syndrome, 7.1- to 8.7-MB
MedGen UID:
462208
Concept ID:
C3150858
Disease or Syndrome
The chromosome 16p12.2-p11.2 deletion syndrome is characterized phenotypically by dysmorphic facial features, feeding difficulties, recurrent ear infections, developmental delay, and cognitive impairment. Additional features, such as heart defects and short stature, are variable (Ballif et al., 2007; Battaglia et al., 2009). The pericentric region of chromosome 16, specifically involving 16p12-p11, is a structurally complex region enriched in repetitive sequence elements, rendering this region susceptible to deletion or rearrangement (Ballif et al., 2007). There are several phenotypes associated with variation in this region: see 611913 for a deletion or duplication at 16p11.2 associated with autism; see 136570 for discussion of a recurrent 520-kb deletion at 16p12.1 associated with developmental delay and craniofacial dysmorphism; and see 613444 for a 220-kb deletion at 16p11.2 associated with isolated severe early-onset obesity and obesity with developmental delay. Battaglia et al. (2009) emphasized that the region at chromosome 16p11.2 that confers susceptibility to autism (AUTS14; see 611913) is located more centromeric to and is distinct from the 16p12.2-p11.2 region involved in the multiple congenital anomalies and intellectual disability phenotype.
Chromosome 17q11.2 deletion syndrome, 1.4-mb
MedGen UID:
462278
Concept ID:
C3150928
Disease or Syndrome
Approximately 5 to 20% of all patients with neurofibromatosis type I (162200) carry a heterozygous deletion of approximately 1.4 Mb involving the NF1 gene and contiguous genes lying in its flanking regions (Riva et al., 2000; Jenne et al., 2001), which is caused by nonallelic homologous recombination of NF1 repeats A and C (Dorschner et al., 2000). The 'NF1 microdeletion syndrome' is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, mental retardation, developmental delay, an excessive number of early-onset neurofibromas (Venturin et al., 2004), and an increased risk for malignant peripheral nerve sheath tumors (De Raedt et al., 2003).
LEOPARD syndrome 3
MedGen UID:
462321
Concept ID:
C3150971
Disease or Syndrome
Multiple lentigines syndrome (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. The characteristic features associated with the condition include brown skin spots called lentigines that are similar to freckles, abnormalities in the electrical signals that control the heartbeat, widely spaced eyes (ocular hypertelorism), a narrowing of the artery from the heart to the lungs (pulmonary stenosis), abnormalities of the genitalia, short stature, and hearing loss. These features vary, however, even among affected individuals in the same family. Not all individuals affected with multiple lentigines syndrome have all the characteristic features of this condition. The lentigines seen in multiple lentigines syndrome typically first appear in mid-childhood, mostly on the face, neck, and upper body. Affected individuals may have thousands of brown skin spots by the time they reach puberty. Unlike freckles, the appearance of lentigines has nothing to do with sun exposure. In addition to lentigines, people with this condition may have lighter brown skin spots called café-au-lait spots. Café-au-lait spots tend to develop before the lentigines, appearing within the first year of life in most affected people. Abnormal electrical signaling in the heart can be a sign of other heart problems. Of the people with multiple lentigines syndrome who have heart problems, about 80 percent have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. The hypertrophic cardiomyopathy in affected individuals most often affects the lower left chamber of the heart (the left ventricle). Up to 20 percent of people with multiple lentigines syndrome who have heart problems have pulmonary stenosis. People with multiple lentigines syndrome can have a distinctive facial appearance. In addition to ocular hypertelorism, affected individuals may have droopy eyelids (ptosis), thick lips, and low-set ears. Abnormalities of the genitalia occur most often in males with multiple lentigines syndrome. The most common abnormality in affected males is undescended testes (cryptorchidism). Other males may have a urethra that opens on the underside of the penis (hypospadias). Males with multiple lentigines syndrome may have a reduced ability to have biological children (decreased fertility). Females with multiple lentigines syndrome may have poorly developed ovaries and delayed puberty. At birth, people with multiple lentigines syndrome are typically of normal weight and height, but in some, growth slows over time. This slow growth results in short stature in 50 to 75 percent of people with multiple lentigines syndrome. Approximately 20 percent of individuals with multiple lentigines syndrome develop hearing loss. This hearing loss is caused by abnormalities in the inner ear (sensorineural deafness) and can be present from birth or develop later in life. Other signs and symptoms of multiple lentigines syndrome include learning disorders, mild developmental delay, a sunken or protruding chest, and extra folds of skin on the back of the neck. Many of the signs and symptoms of multiple lentigines syndrome also occur in a similar disorder called Noonan syndrome. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life.
Chromosome 7q11.23 deletion syndrome, distal, 1.2-mb
MedGen UID:
462349
Concept ID:
C3150999
Disease or Syndrome
Hemizygous 1.2-Mb deletion of the distal region of chromosome 7q11.23 is associated with increased risk for epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities (Ramocki et al., 2010).
Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia
MedGen UID:
477107
Concept ID:
C3275476
Disease or Syndrome
Chromosome Xq27.3-q28 duplication syndrome
MedGen UID:
477152
Concept ID:
C3275521
Disease or Syndrome
Chromosome Xq27.3-q28 duplication syndrome is an X-linked recessive neurodevelopmental disorder characterized by mild mental retardation, mild facial dysmorphism, short stature, and primary testicular failure manifest as high-pitched voice, sparse body hair, abdominal obesity, and small testes. Female carriers may have short stature and premature ovarian failure (summary by Rio et al., 2010).
Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 2
MedGen UID:
481329
Concept ID:
C3279699
Disease or Syndrome
Chromosome 8q21.11 deletion syndrome
MedGen UID:
481861
Concept ID:
C3280231
Disease or Syndrome
The chromosome 8q21.11 deletion syndrome is characterized by intellectual disability and common facial dysmorphic features (summary by Palomares et al., 2011).
AMELOGENESIS IMPERFECTA AND GINGIVAL FIBROMATOSIS SYNDROME
MedGen UID:
481906
Concept ID:
C3280276
Disease or Syndrome
Amelogenesis imperfecta and gingival fibromatosis syndrome is an autosomal recessive condition characterized by mild gingival fibromatosis and dental anomalies, including hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay of tooth eruption, hypodontia/oligodontia, pericoronal radiolucencies, and unerupted teeth (Martelli-Junior et al., 2008).
Cognitive impairment with or without cerebellar ataxia
MedGen UID:
482045
Concept ID:
C3280415
Disease or Syndrome
Chromosome 17q12 duplication syndrome
MedGen UID:
482767
Concept ID:
C3281137
Disease or Syndrome
Chromosome 17q12 deletion syndrome
MedGen UID:
482768
Concept ID:
C3281138
Disease or Syndrome
Epileptic encephalopathy, early infantile, 1
MedGen UID:
483052
Concept ID:
C3463992
Disease or Syndrome
Early infantile epileptic encephalopathy is a severe form of epilepsy first reported by Ohtahara et al. (1976). It is characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Approximately 75% of EIEE patients progress to 'West syndrome,' which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG (Kato et al., 2007). Deprez et al. (2009) reviewed the genetics of epilepsy syndromes starting in the first year of life and included a diagnostic algorithm. EIEE1 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1) to syndromic (309510) and nonsyndromic (300419) mental retardation. Although males with ARX mutations are often more severely affected, female mutation carriers may also be affected (Kato et al., 2004; Wallerstein et al., 2008). Genetic Heterogeneity of Early Infantile Epileptic Encephalopathy EIEE is a genetically heterogeneous disorder. See EIEE2 (300672), caused by mutation in the CDKL5 gene (300203); EIEE3 (609304), caused by mutation in the SLC25A22 gene (609302); EIEE4 (612164), caused by mutation in the STXBP1 gene (602926); EIEE5 (613477), caused by mutation in the SPTAN1 gene (182810); EIEE6 (607208), also known as Dravet syndrome, caused by mutation in the SCN1A gene (182389); EIEE7 (613720), caused by mutation in the KCNQ2 gene (602235); EIEE8 (300607), caused by mutation in the ARHGEF9 gene (300429); EIEE9 (300088), caused by mutation in the PCDH19 gene (300460); EIEE10 (613402), caused by mutation in the PNKP gene (605610); EIEE11 (613721), caused by mutation in the SCN2A gene (182390); EIEE12 (613722), caused by mutation in the PLCB1 gene (607120); EIEE13 (614558), caused by mutation in the SCN8A gene (600702); EIEE14 (614959), caused by mutation in the KCNT1 gene (608167); EIEE15 (615006), caused by mutation in the ST3GAL3 gene (606494); EIEE16 (615338), caused by mutation in the TBC1D24 gene (613577); EIEE17 (615473), caused by mutation in the GNAO1 gene (139311); EIEE18 (615476), caused by mutation in the SZT2 gene (615463); EIEE19 (615744), caused by mutation in the GABRA1 gene (137160); EIEE20 (300868), caused by mutation in the PIGA gene (311770); EIEE21 (615833), caused by mutation in the NECAP1 gene (611623); EIEE22 (300896), caused by mutation in the SLC35A2 gene (314375); EIEE23 (615859), caused by mutation in the DOCK7 gene (615730); EIEE24 (615871), caused by mutation in the HCN1 gene (602780); EIEE25 (615905), caused by mutation in the SLC13A5 gene (608305); EIEE26 (616056), caused by mutation in the KCNB1 gene (600397); EIEE27 (616139), caused by mutation in the GRIN2B gene (138252); EIEE28 (616211), caused by mutation in the WWOX gene (605131); EIEE29 (616339), caused by mutation in the AARS gene (601065); EIEE30 (616341), caused by mutation in the SIK1 gene (605705); EIEE31 (616346), caused by mutation in the DNM1 gene (602377); EIEE32 (616366), caused by mutation in the KCNA2 gene (176262); and EIEE33 (616409), caused by mutation in the EEF1A2 gene (602959). The phenotype is also observed in other genetic disorders, including GLUT1 deficiency syndrome (606777); glycine encephalopathy (605899); Aicardi-Goutieres syndrome (225750); and in males with MECP2 mutations (300673), among others. For associations pending confirmation, see MOLECULAR GENETICS.
Deficiency of aminoacyl-histidine dipeptidase
MedGen UID:
501203
Concept ID:
C3495555
Disease or Syndrome
Spastic paraplegia 55, autosomal recessive
MedGen UID:
761342
Concept ID:
C3539506
Disease or Syndrome
Spastic paraplegia 56, autosomal recessive
MedGen UID:
761343
Concept ID:
C3539507
Disease or Syndrome
SPG56 is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive lower-limb spasticity resulting in walking difficulties. Upper limbs are often also affected, and some patients may have a subclinical axonal neuropathy (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Combined oxidative phosphorylation deficiency 10
MedGen UID:
766443
Concept ID:
C3553529
Disease or Syndrome
COXPD10 is an autosomal recessive disorder resulting in variable defects of mitochondrial oxidative respiration. Affected individuals present in infancy with hypertrophic cardiomyopathy and lactic acidosis. The severity is variable, but can be fatal in the most severe cases (summary by Ghezzi et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Epilepsy, nocturnal frontal lobe, 5
MedGen UID:
767220
Concept ID:
C3554306
Disease or Syndrome
Nocturnal frontal lobe epilepsy-5 is an autosomal dominant focal epilepsy syndrome characterized by childhood onset of clusters of motor seizures during sleep. Some patients may develop behavioral or psychiatric manifestations and/or intellectual disability. The phenotype is more severe than observed in other genetic forms of ENFL (summary by Heron et al., 2012). For a general description and a discussion of genetic heterogeneity of ENFL, see ENFL1 (600513).
Mitochondrial complex III deficiency, nuclear type 2
MedGen UID:
767519
Concept ID:
C3554605
Disease or Syndrome
Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life (summary by Ghezzi et al., 2011). The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances (Morino et al., 2014; Atwal, 2014; Nogueira et al., 2013). For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).
Craniosynostosis 3
MedGen UID:
811568
Concept ID:
C3715051
Disease or Syndrome
Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (Fitzpatrick, 2013). Mutation in the TCF12 gene has been found to several forms of craniosynostosis including coronal, sagittal, and multisuture. For discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
Cystic fibrosis with helicobacter pylori gastritis, megaloblastic anemia and subnormal mentality
MedGen UID:
812585
Concept ID:
C3806255
Disease or Syndrome
Mental retardation, X-linked 98
MedGen UID:
813060
Concept ID:
C3806730
Disease or Syndrome
Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type)
MedGen UID:
815773
Concept ID:
C3809443
Disease or Syndrome
Mitochondrial DNA depletion syndrome-12 is an autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance and, in some patients, muscle weakness and atrophy. Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and accumulation of abnormal mitochondria (summary by Echaniz-Laguna et al., 2012). For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).

Recent clinical studies

Etiology

Wang T, Chen K, Li H, Dong S, Su N, Liu Y, Cheng Y, Dai J, Yang C, Xiao S
J Clin Psychiatry 2015 Feb;76(2):135-41. doi: 10.4088/JCP.13m08812. PMID: 25742200
Moon JH, Lim S, Han JW, Kim KM, Choi SH, Park KS, Kim KW, Jang HC
Stroke 2015 Apr;46(4):1024-30. Epub 2015 Mar 3 doi: 10.1161/STROKEAHA.114.008170. [Epub ahead of print] PMID: 25737314
Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM, Larvie M, Amariglio RE, Marshall GA, Rentz DM, Johnson KA, Sperling RA
Brain 2015 Apr;138(Pt 4):1023-35. Epub 2015 Feb 11 doi: 10.1093/brain/awv007. [Epub ahead of print] PMID: 25678559Free PMC Article
Kirkpatrick AC, Vincent AS, Guthery L, Prodan CI
Am J Med 2014 Dec;127(12):1243-6. Epub 2014 Aug 26 doi: 10.1016/j.amjmed.2014.08.010. [Epub ahead of print] PMID: 25168078
Law LL, Barnett F, Yau MK, Gray MA
Age Ageing 2014 Nov;43(6):813-20. Epub 2014 May 21 doi: 10.1093/ageing/afu055. [Epub ahead of print] PMID: 24850540

Diagnosis

Wang T, Chen K, Li H, Dong S, Su N, Liu Y, Cheng Y, Dai J, Yang C, Xiao S
J Clin Psychiatry 2015 Feb;76(2):135-41. doi: 10.4088/JCP.13m08812. PMID: 25742200
Moon JH, Lim S, Han JW, Kim KM, Choi SH, Park KS, Kim KW, Jang HC
Stroke 2015 Apr;46(4):1024-30. Epub 2015 Mar 3 doi: 10.1161/STROKEAHA.114.008170. [Epub ahead of print] PMID: 25737314
Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM, Larvie M, Amariglio RE, Marshall GA, Rentz DM, Johnson KA, Sperling RA
Brain 2015 Apr;138(Pt 4):1023-35. Epub 2015 Feb 11 doi: 10.1093/brain/awv007. [Epub ahead of print] PMID: 25678559Free PMC Article
Kirkpatrick AC, Vincent AS, Guthery L, Prodan CI
Am J Med 2014 Dec;127(12):1243-6. Epub 2014 Aug 26 doi: 10.1016/j.amjmed.2014.08.010. [Epub ahead of print] PMID: 25168078
Law LL, Barnett F, Yau MK, Gray MA
Age Ageing 2014 Nov;43(6):813-20. Epub 2014 May 21 doi: 10.1093/ageing/afu055. [Epub ahead of print] PMID: 24850540

Therapy

Wang T, Chen K, Li H, Dong S, Su N, Liu Y, Cheng Y, Dai J, Yang C, Xiao S
J Clin Psychiatry 2015 Feb;76(2):135-41. doi: 10.4088/JCP.13m08812. PMID: 25742200
Kirkpatrick AC, Vincent AS, Guthery L, Prodan CI
Am J Med 2014 Dec;127(12):1243-6. Epub 2014 Aug 26 doi: 10.1016/j.amjmed.2014.08.010. [Epub ahead of print] PMID: 25168078
Law LL, Barnett F, Yau MK, Gray MA
Age Ageing 2014 Nov;43(6):813-20. Epub 2014 May 21 doi: 10.1093/ageing/afu055. [Epub ahead of print] PMID: 24850540
Rizzo MR, Barbieri M, Boccardi V, Angellotti E, Marfella R, Paolisso G
J Gerontol A Biol Sci Med Sci 2014 Sep;69(9):1122-31. Epub 2014 Mar 26 doi: 10.1093/gerona/glu032. [Epub ahead of print] PMID: 24671867
Guo JL, Tsai YY, Liao JY, Tu HM, Huang CM
Int J Geriatr Psychiatry 2014 Jul;29(7):661-9. Epub 2013 Dec 7 doi: 10.1002/gps.4056. [Epub ahead of print] PMID: 24318959

Prognosis

Moon JH, Lim S, Han JW, Kim KM, Choi SH, Park KS, Kim KW, Jang HC
Stroke 2015 Apr;46(4):1024-30. Epub 2015 Mar 3 doi: 10.1161/STROKEAHA.114.008170. [Epub ahead of print] PMID: 25737314
Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM, Larvie M, Amariglio RE, Marshall GA, Rentz DM, Johnson KA, Sperling RA
Brain 2015 Apr;138(Pt 4):1023-35. Epub 2015 Feb 11 doi: 10.1093/brain/awv007. [Epub ahead of print] PMID: 25678559Free PMC Article
Ma L, Feng M, Qian Y, Yang W, Liu J, Han R, Zhu H, Li Y
Yonsei Med J 2015 Jan;56(1):89-94. doi: 10.3349/ymj.2015.56.1.89. PMID: 25510751Free PMC Article
Kang Y, Kim M, Jung D, Cha C, Kim M
Int Nurs Rev 2014 Sep;61(3):318-26. Epub 2014 Jul 11 doi: 10.1111/inr.12116. [Epub ahead of print] PMID: 25039493
Rizzo MR, Barbieri M, Boccardi V, Angellotti E, Marfella R, Paolisso G
J Gerontol A Biol Sci Med Sci 2014 Sep;69(9):1122-31. Epub 2014 Mar 26 doi: 10.1093/gerona/glu032. [Epub ahead of print] PMID: 24671867

Clinical prediction guides

Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM, Larvie M, Amariglio RE, Marshall GA, Rentz DM, Johnson KA, Sperling RA
Brain 2015 Apr;138(Pt 4):1023-35. Epub 2015 Feb 11 doi: 10.1093/brain/awv007. [Epub ahead of print] PMID: 25678559Free PMC Article
Ma L, Feng M, Qian Y, Yang W, Liu J, Han R, Zhu H, Li Y
Yonsei Med J 2015 Jan;56(1):89-94. doi: 10.3349/ymj.2015.56.1.89. PMID: 25510751Free PMC Article
Kirkpatrick AC, Vincent AS, Guthery L, Prodan CI
Am J Med 2014 Dec;127(12):1243-6. Epub 2014 Aug 26 doi: 10.1016/j.amjmed.2014.08.010. [Epub ahead of print] PMID: 25168078
Robinson JL, Molina-Porcel L, Corrada MM, Raible K, Lee EB, Lee VM, Kawas CH, Trojanowski JQ
Brain 2014 Sep;137(Pt 9):2578-87. Epub 2014 Jul 9 doi: 10.1093/brain/awu190. [Epub ahead of print] PMID: 25012223Free PMC Article
Rizzo MR, Barbieri M, Boccardi V, Angellotti E, Marfella R, Paolisso G
J Gerontol A Biol Sci Med Sci 2014 Sep;69(9):1122-31. Epub 2014 Mar 26 doi: 10.1093/gerona/glu032. [Epub ahead of print] PMID: 24671867

Recent systematic reviews

Wefel JS, Kesler SR, Noll KR, Schagen SB
CA Cancer J Clin 2015 Mar;65(2):123-38. Epub 2014 Dec 5 doi: 10.3322/caac.21258. [Epub ahead of print] PMID: 25483452Free PMC Article
Lee M, Saver JL, Hong KS, Wu YL, Liu HC, Rao NM, Ovbiagele B
CMAJ 2014 Oct 7;186(14):E536-46. Epub 2014 Aug 25 doi: 10.1503/cmaj.140147. [Epub ahead of print] PMID: 25157064Free PMC Article
de Jonghe A, van de Glind EM, van Munster BC, de Rooij SE
J Psychosom Res 2014 Mar;76(3):193-9. Epub 2013 Dec 31 doi: 10.1016/j.jpsychores.2013.12.007. [Epub ahead of print] PMID: 24529037
Guo JL, Tsai YY, Liao JY, Tu HM, Huang CM
Int J Geriatr Psychiatry 2014 Jul;29(7):661-9. Epub 2013 Dec 7 doi: 10.1002/gps.4056. [Epub ahead of print] PMID: 24318959
Howe AS
Clin Neurophysiol 2014 Jun;125(6):1145-51. Epub 2013 Nov 1 doi: 10.1016/j.clinph.2013.10.019. [Epub ahead of print] PMID: 24252395

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