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Cryptorchidism

MedGen UID:
504309
Concept ID:
CN000029
Finding
Synonyms: Undescended testes; Undescended testis
 
HPO: HP:0000028

Definition

Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the testis. [from HPO]

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.
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.
Beckwith-Wiedemann syndrome
MedGen UID:
2562
Concept ID:
C0004903
Congenital Abnormality
Beckwith-Wiedemann syndrome (BWS) is a growth disorder characterized by macrosomia, macroglossia, visceromegaly, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical cytomegaly, and renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly). Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.
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.
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.
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.
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).
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.
Laurence-Moon syndrome
MedGen UID:
44078
Concept ID:
C0023138
Disease or Syndrome
A rare genetic syndrome with an autosomal recessive pattern of inheritance. Mutations in the BBS5 and MKKS genes of chromosome 11 have been observed in some cases which has lead to comparisons with Bardet-Biedl syndrome and McKusick-Kaufman syndrome. These syndromes have similar etiologies and presentations but are considered separate entities. Clinical signs of Laurence-Moon syndrome include ataxia, intellectual delay, retinitis pigmentosa and hypogonadism. The clinical course follows a progression to growth retardation, spastic paraplegia and optic atrophy with eventual vision loss.
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.
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.
Prader-Willi syndrome
MedGen UID:
46057
Concept ID:
C0032897
Congenital Abnormality
Prader-Willi (PWS) syndrome is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). Motor milestones and language development are delayed. All individuals have some degree of cognitive impairment. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common; characteristic facial features, strabismus, and scoliosis are often present, and non-insulin-dependent diabetes mellitus often occurs in obese individuals.
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).
Rubinstein-Taybi syndrome
MedGen UID:
48517
Concept ID:
C0035934
Disease or Syndrome
Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and great toes, short stature, and moderate to severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal; however, height, weight, and head circumference percentiles rapidly drop in the first few months of life. Obesity may occur in childhood or adolescence. IQ scores range from 25 to 79; average IQ is between 36 and 51. Other variable findings are coloboma, cataract, congenital heart defects, renal abnormalities, and cryptorchidism.
Tetralogy of Fallot
MedGen UID:
21498
Concept ID:
C0039685
Congenital Abnormality
Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth. Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment. Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death. Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities. People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.
Noonan syndrome 1
MedGen UID:
22527
Concept ID:
C0041409
Disease or Syndrome
Noonan syndrome (NS) is characterized by short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, characteristic facies, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one third of affected individuals have mild intellectual disability.
Zellweger syndrome
MedGen UID:
21958
Concept ID:
C0043459
Congenital Abnormality
Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD, ZSS) is a continuum of three phenotypes — Zellweger syndrome (ZS), the most severe; neonatal adrenoleukodystrophy (NALD); and infantile Refsum disease (IRD), the least severe — that were originally described before the biochemical and molecular bases of these disorders had been fully determined. Individuals with PBD, ZSS usually come to clinical attention in the newborn period or later in childhood. In the newborn period, affected children are hypotonic, feed poorly, and have distinctive facies, seizures, and liver cysts with hepatic dysfunction. Bony stippling (chondrodysplasia punctata) of the patella(e) and other long bones may occur. Infants with ZS are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Older children have retinal dystrophy, sensorineural hearing loss, developmental delay with hypotonia, and liver dysfunction. The clinical courses of NALD and IRD are variable and may include developmental delays, hearing loss, vision impairment, liver dysfunction, episodes of hemorrhage, and intracranial bleeding. While some children can be very hypotonic, others learn to walk and talk. The condition is often slowly progressive.
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.
Malignant tumor of testis
MedGen UID:
56313
Concept ID:
C0153594
Neoplastic Process
Testicular germ cell tumors (TGCTs) affect 1 in 500 men and are the most common cancer in males aged 15 to 40 in western European populations. The incidence of TGCT rose dramatically during the 20th century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT, and a family history of the disease. Brothers of men with TGCT have an 8- to 10-fold risk of developing TGCT, whereas the relative risk to fathers and sons is 4-fold. This familial relative risk is much higher than that for most other types of cancer (summary by Rapley et al., 2000). Genetic Heterogeneity of Testicular Germ Cell Tumors A locus for testicular germ cell tumors (TGCT1; 300228) has been identified on chromosome Xq27.
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).
Smith-Lemli-Opitz syndrome
MedGen UID:
61231
Concept ID:
C0175694
Disease or Syndrome
Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple anomaly syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase. It is characterized by prenatal and postnatal growth retardation, microcephaly, moderate to severe intellectual disability, and multiple major and minor malformations. The malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes. The clinical spectrum is wide and individuals have been described with normal development and only minor malformations.
Opitz-Frias syndrome
MedGen UID:
104493
Concept ID:
C0175696
Disease or Syndrome
X-linked Opitz G/BBB syndrome (XLOS) is a multiple congenital anomaly disorder characterized by facial anomalies (ocular hypertelorism, prominent forehead, widow's peak, broad nasal bridge, anteverted nares), laryngotracheoesophageal defects, and genitourinary abnormalities (hypospadias, cryptorchidism, and hypoplastic/bifid scrotum). Developmental delay and intellectual disability are observed in about 50% of affected males. Cleft lip and/or palate are present in approximately 50% of affected individuals. Other malformations present in fewer than 50% of individuals include congenital heart defects, imperforate or ectopic anus, and midline brain defects (Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis). Wide clinical variability occurs even among members of the same family. Female carriers usually manifest only ocular hypertelorism.
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.
Aarskog syndrome
MedGen UID:
61234
Concept ID:
C0175701
Congenital Abnormality
Aarskog-Scott syndrome, also known as faciogenital dysplasia, is an X-linked disorder characterized by short stature, hypertelorism, shawl scrotum, and brachydactyly, although there is wide phenotypic variability and other features, such as joint hyperextensibility, short nose, widow's peak, and inguinal hernia, may also occur. Most patients do not have mental retardation, but some may have neurobehavioral features. Carrier females may present with subtle features, such as widow's peak or short stature (summary by Orrico et al., 2010).
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.
LEOPARD syndrome
MedGen UID:
104494
Concept ID:
C0175704
Disease or Syndrome
LEOPARD syndrome (LS) is an acronym for the cardinal features lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with LS do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (HCM) (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth retardation resulting in short stature occurs in fewer than 50% of affected persons. Sensorineural hearing deficits, present in approximately 20%, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with LS.
11p partial monosomy syndrome
MedGen UID:
64512
Concept ID:
C0206115
Disease or Syndrome
Aniridia is characterized by complete or partial iris hypoplasia usually (but not always) with associated foveal hypoplasia resulting in reduced visual acuity and nystagmus presenting in early infancy. Frequently associated ocular abnormalities (often of later onset) include cataract, glaucoma, and corneal opacification and vascularization. Aniridia may occur either as an isolated ocular abnormality without systemic involvement, caused by mutation of PAX6 or deletion of a regulatory region controlling its expression, or as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome, with a deletion of 11p13 involving the PAX6 (aniridia) locus and the adjacent WT1 (Wilms tumor) locus. Individuals with deletion of PAX6 and WT1 are at up to a 50% risk of developing Wilms tumor.
Acrodysostosis
MedGen UID:
113097
Concept ID:
C0220659
Disease or Syndrome
Acrodysostosis-1 is a form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin (summary by Linglart et al., 2011). However, not all patients show endocrine abnormalities (Lee et al., 2012). Genetic Heterogeneity of Acrodysostosis See also ACRDYS2 (614613), caused by mutation in the PDE4D gene (600129) on chromosome 5q12.
Arthrogryposis multiplex congenita distal type 1
MedGen UID:
113099
Concept ID:
C0220662
Congenital Abnormality
The distal arthrogryposes are a group of disorders that mainly involve the distal parts of the limbs. They are characterized by congenital contractures of 2 or more different body areas without a primary neurologic or muscle disease. The prototypic distal arthrogryposis is type 1 (DA1), which is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected. While the pattern of affected joints is consistent, the degree to which the joints are affected is highly variable, with equinovarus deformities ranging from mild to severe and hand involvement ranging from isolated hypoplasia of the distal interphalangeal crease of the fifth digit to severely clenched fists and ulnar deviation of the wrist. The various phenotypic forms of distal arthrogryposis are classified hierarchically according to the proportion of features they share with one another and are designated DA1 through DA10 (summary by Bamshad et al., 2009). Genetic Heterogeneity of Distal Arthrogryposes Distal arthrogryposis type 1 includes DA1A, caused by mutation in the TPM2 gene, and DA1B (614335), caused by mutation in the MYBPC1 gene (160794) on chromosome 12q23.2. Other forms include DA2A (Freeman-Sheldon syndrome, 193700), caused by mutation in the MYH3 gene (160720) on chromosome 17p13.1; DA2B (Sheldon-Hall syndrome, 601680), caused by mutation in MYH3, the TNNT3 gene (600692) on chromosome 11p15.5, the TNNI2 gene (191043), also on 11p15.5, or TPM2 (190990) on chromosome 9p13; DA3 (Gordon syndrome, 114300) and DA5 (108145), caused by mutation in the PIEZO2 gene (613629) on chromosome 18p11; DA4 (609128); DA5D (615065), caused by mutation in the ECEL1 gene (605896) on chromosome 2q36; DA6 (108200); DA7 (158300), caused by mutation in the MYH8 gene (160741) on chromosome 17p13.1; DA8 (178110); DA9 (121050), caused by mutation in the FBN2 gene (612570) on chromosome 5q23-q31; and DA10 (187370), which maps to chromosome 2q. See 277720 for discussion of a possible autosomal recessive form of DA2A. See 208155 for a description of Illum syndrome, which includes 'whistling face,' central nervous system dysfunction, and calcium deposition in central nervous system and muscle.
Gordon's syndrome
MedGen UID:
66314
Concept ID:
C0220666
Congenital Abnormality
DA3, or Gordon syndrome, is distinguished from other distal arthrogryposes by short stature and cleft palate (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA3 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 5 (DA5; 108145) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of ocular abnormalities and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders may represent variable expressivity of the same condition. For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
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.
VATER association
MedGen UID:
67396
Concept ID:
C0220708
Congenital Abnormality
VATER is a mnemonically useful acronym for the nonrandom association of vertebral defects (V), anal atresia (A), tracheoesophageal fistula with esophageal atresia (TE), and radial or renal dysplasia (R). This combination of associated defects was pointed out by Quan and Smith (1972). Nearly all cases have been sporadic. VACTERL is an acronym for an expanded definition of the association that includes cardiac malformations (C) and limb anomalies (L). The VACTERL association is a spectrum of various combinations of its 6 components, which can be a manifestation of several recognized disorders rather than a distinct anatomic or etiologic entity (Khoury et al., 1983). Also see VATER/VACTERL association with hydrocephalus (VACTERL-H; 276950) and VACTERL with or without hydrocephalus (VACTERLX; 314390).
Diastrophic dysplasia
MedGen UID:
113103
Concept ID:
C0220726
Congenital Abnormality
Diastrophic dysplasia (DTD) is characterized by limb shortening, normal-sized skull, hitchhiker thumbs, spinal deformities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis), and contractures of the large joints with deformities and early-onset osteoarthritis. Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. On occasion the disease can be lethal at birth, but most affected individuals survive the neonatal period and develop physical limitations with normal intelligence.
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.
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).
FG syndrome
MedGen UID:
113106
Concept ID:
C0220769
Disease or Syndrome
The phenotypic spectrum of MED12-related disorders, which is still being defined, includes at a minimum the phenotypes of FG syndrome type 1 (FGS1) and Lujan syndrome (LS). FGS1 and LS share the clinical findings of cognitive impairment, hypotonia, and abnormalities of the corpus callosum. FGS1 is further characterized by absolute or relative macrocephaly, tall forehead, downslanted palpebral fissures, small and simple ears, constipation and/or anal anomalies, broad thumbs and halluces, and characteristic behavior. LS is further characterized by large head, tall thin body habitus, long thin face, high nasal root, high narrow palate, and short philtrum. Carrier females in families with FGS1 and LS are typically unaffected.
Treacher Collins syndrome
MedGen UID:
66078
Concept ID:
C0242387
Congenital Abnormality
Treacher Collins syndrome (TCS) is characterized by hypoplasia of the zygomatic bones and mandible, external ear abnormalities, coloboma (notching) of the lower eyelid, absence of the lower eyelashes, and preauricular hair displacement onto the cheeks. About 40%-50% of individuals have conductive hearing loss attributed most commonly to malformation (including ankylosis, hypoplasia, or absence) of the ossicles and hypoplasia of the middle ear cavities. Inner ear structures tend to be normal. Other less common abnormalities include cleft palate with or without cleft lip and unilateral or bilateral choanal stenosis or atresia.
Seckel syndrome
MedGen UID:
78534
Concept ID:
C0265202
Disease or Syndrome
A syndrome of proportionate dwarfism, delayed mental development, microcephaly, and typical facial appearance marked by a birdlike protrusion of midfacial structures.
Robinow syndrome
MedGen UID:
78535
Concept ID:
C0265205
Disease or Syndrome
Robinow syndrome is a genetically heterogeneous disorder characterized by mesomelic limb shortening associated with facial and genital abnormalities (Robinow et al., 1969). Both autosomal dominant and autosomal recessive (268310) forms have been described; the recessive form is caused by mutations in the ROR2 gene (602337).
Weaver syndrome
MedGen UID:
120511
Concept ID:
C0265210
Congenital Abnormality
Weaver syndrome comprises pre- and postnatal overgrowth, accelerated osseous maturation, characteristic craniofacial appearance, and developmental delay. Most cases are sporadic, although autosomal dominant inheritance has been reported. Although there is phenotypic overlap between Weaver syndrome and Sotos syndrome (117550), distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand in Weaver syndrome, whereas in Sotos syndrome carpal bone development is at or behind that of the rest of the hand (summary by Basel-Vanagaite, 2010). The 'Weaver-like' syndrome reported by Stoll et al. (1985) in a mother and son may be a separate entity. Sotos syndrome (117550), which shows considerable phenotypic overlap with Weaver syndrome, is caused by mutation in the NSD1 gene (601573) on chromosome 5q35.
Meckel-Gruber syndrome
MedGen UID:
120513
Concept ID:
C0265215
Congenital Abnormality
A rare, lethal, autosomal recessive inherited syndrome characterized by pulmonary hypoplasia, central nervous system malformations, and hepatic malformations.
Neu-Laxova syndrome
MedGen UID:
78537
Concept ID:
C0265218
Congenital Abnormality
Neu-Laxova syndrome is an autosomal recessive lethal multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, central nervous system anomalies (lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum), limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears (summary by Manning et al., 2004). Genetic Heterogeneity of Neu-Laxova Syndrome NLS2 (616038) is caused by mutation in the PSAT1 gene (610936) on chromosome 9q21.
Miller Dieker syndrome
MedGen UID:
78538
Concept ID:
C0265219
Disease or Syndrome
LIS1-associated lissencephaly includes Miller-Dieker syndrome (MDS), isolated lissencephaly sequence (ILS), and (rarely) subcortical band heterotopia (SBH). Lissencephaly and SBH are cortical malformations caused by deficient neuronal migration during embryogenesis. Lissencephaly refers to a "smooth brain" with absent gyri (agyria) or abnormally wide gyri (pachygyria). SBH refers to a band of heterotopic gray matter located just beneath the cortex and separated from it by a thin zone of normal white matter. MDS is characterized by lissencephaly, typical facial features, and severe neurologic abnormalities. ILS is characterized by lissencephaly and its direct sequelae: developmental delay, intellectual disability, and seizures.
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.
Freeman-Sheldon syndrome
MedGen UID:
120516
Concept ID:
C0265224
Congenital Abnormality
Freeman-Sheldon syndrome (FSS), or DA2A, is phenotypically similar to DA1. In addition to contractures of the hands and feet, FSS is characterized by oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice (often only a few millimeters in diameter at birth), puckered lips, and an H-shaped dimple of the chin; hence, FSS has been called 'whistling face syndrome.' The limb phenotypes of DA1 and FSS may be so similar that they can only be distinguished by the differences in facial morphology (summary by Bamshad et al., 2009).
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).
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.
Miller syndrome
MedGen UID:
120522
Concept ID:
C0265257
Disease or Syndrome
Miller syndrome, or postaxial acrofacial dysostosis, is a rare autosomal recessive disorder characterized clinically by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the postaxial elements of the limbs, coloboma of the eyelids, and supernumerary nipples (summary by Ng et al., 2010).
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
MedGen UID:
82696
Concept ID:
C0265261
Congenital Abnormality
A rare syndrome of short stature, abnormal facies and webbing of the neck, antecubital, digital, popliteal, and intercural areas. Joint contractures, vertebral fusion defects, and rocker-bottom feet are usually associated.
Femoral hypoplasia - unusual facies syndrome
MedGen UID:
120523
Concept ID:
C0265263
Disease or Syndrome
Femoral-facial syndrome (FFS), also known as femoral hypoplasia-unusual facies syndrome (FHUFS), is a rare and sporadic multiple congenital anomaly syndrome comprising bilateral femoral hypoplasia and characteristic facial features, such as long philtrum, thin upper lip, micrognathia with or without cleft palate, upward-slanting palpebral fissures, and a short nose with broad tip. Other features, such as renal anomalies, are more variable (summary by Nowaczyk et al., 2010).
Atelosteogenesis type 1
MedGen UID:
82701
Concept ID:
C0265283
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.
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.
Coffin-Siris syndrome
MedGen UID:
75565
Concept ID:
C0265338
Congenital Abnormality
Coffin-Siris syndrome (CSS) is characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth digit, distinctive facial features, and moderate to severe developmental/cognitive delay. Expressive language is more severely affected than receptive language. On average, children with CSS learn to sit at 12 months, walk at 30 months, and speak their first words at 24 months. Other findings commonly include failure to thrive, feeding difficulties, short stature, ophthalmologic abnormalities, microcephaly, brain malformations, and hearing loss.
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.
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.
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).
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.
Testosterone 17-beta-dehydrogenase deficiency
MedGen UID:
120626
Concept ID:
C0268296
Disease or Syndrome
17-beta hydroxysteroid dehydrogenase 3 deficiency is a condition that affects male sexual development. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of the male sex hormone testosterone. Testosterone has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth. Most people with 17-beta hydroxysteroid dehydrogenase 3 deficiency are born with external genitalia that appear female. In some cases, the external genitalia do not look clearly male or clearly female (sometimes called ambiguous genitalia). Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) or the urethra opening on the underside of the penis (hypospadias). During puberty, people with this condition develop some secondary sex characteristics, such as increased muscle mass, deepening of the voice, and development of male pattern body hair. The penis and scrotum (the sac of skin that holds the testes) grow larger during this period. In addition to these changes typical of adolescent boys, some affected males may also experience breast enlargement (gynecomastia). Men with this disorder are generally unable to father children (infertile). Children with 17-beta hydroxysteroid dehydrogenase 3 deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.
3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency
MedGen UID:
75667
Concept ID:
C0268297
Disease or Syndrome
Pseudovaginal perineoscrotal hypospadias is a form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum.
Reifenstein syndrome
MedGen UID:
82785
Concept ID:
C0268301
Disease or Syndrome
A disorder also known as partial androgen insensitivity syndrome (PAIS). These patients exhibit partial resistance to androgenic and metabolic effects of TESTOSTERONE.
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.
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).
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.
De Lange syndrome
MedGen UID:
78752
Concept ID:
C0270972
Congenital Abnormality
Classic Cornelia de Lange syndrome (CdLS) is characterized by distinctive facial features, growth retardation (prenatal onset; <5th centile throughout life), hirsutism, and upper limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, arched eyebrows, long eyelashes, small upturned nose, small widely spaced teeth, and microcephaly. IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS.
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.
Hennekam lymphangiectasia-lymphedema syndrome
MedGen UID:
137946
Concept ID:
C0340834
Congenital Abnormality
Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by generalized lymphatic dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. Additional features of the disorder include facial dysmorphism and cognitive impairment (summary by Alders et al., 2014). Genetic Heterogeneity of Hennekam Lymphangiectasia-Lymphedema Syndrome See also HKLLS2 (616006), caused by mutation in the FAT4 gene (612411) on chromosome 4q28.
Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness
MedGen UID:
83338
Concept ID:
C0342287
Congenital Abnormality
Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Onset of megaloblastic anemia is between infancy and adolescence. The anemia is corrected with pharmacologic doses of thiamine (vitamin B1) (25-75 mg/day compared to US RDA of 1.5 mg/day). However, the red cells remain macrocytic. The anemia can recur when thiamine is withdrawn. Progressive sensorineural hearing loss has generally been early and can be detected in toddlers; hearing loss is irreversible and may not be prevented by thiamine treatment. The diabetes mellitus is non-type I in nature, with age of onset from infancy to adolescence.
Congenital adrenal hypoplasia, X-linked
MedGen UID:
87442
Concept ID:
C0342482
Congenital Abnormality
X-linked adrenal hypoplasia congenita (X-linked AHC) is characterized by infantile-onset acute primary adrenal insufficiency at an average age of three weeks in approximately 60% of affected individuals. Onset in approximately 40% is in childhood. A few individuals present in adulthood with delayed-onset adrenal failure or partial hypogonadism due to partial forms of X-linked AHC. Adrenal insufficiency typically presents acutely in male infants with vomiting, feeding difficulty, dehydration, and shock caused by a salt-wasting episode. Hypoglycemia (sometimes presenting with seizures) or isolated salt loss may be the first symptom of X-linked AHC. Cortisol may be low or within the normal range, which is inappropriately low for a sick child. In older children, adrenal failure may be precipitated by intercurrent illness or stress. If untreated, adrenal insufficiency is rapidly lethal as a result of hyperkalemia, acidosis, hypoglycemia, and shock. Affected males typically have delayed puberty (onset age >14 years) or arrested puberty caused by hypogonadotropic hypogonadism (HH). Early pubertal development with pubertal arrest has been reported in some cases. Males with classic X-linked AHC are infertile despite treatment with exogenous gonadotropin therapy or pulsatile gonadotropin-releasing hormone (GnRH), although testicular sperm extraction-intracytoplasmic sperm injection (TESE-ICSI) has been successful in one case. Carrier females may very occasionally have symptoms of adrenal insufficiency or hypogonadotropic hypogonadism as a result of skewed X-chromosome inactivation.
Branchiooculofacial syndrome
MedGen UID:
91261
Concept ID:
C0376524
Congenital Abnormality
The branchiooculofacial syndrome (BOFS) is characterized by: branchial (cervical [90%] or infra- or supra-auricular [60%]) skin defects that range from barely perceptible thin skin or hair patch to erythematous “hemangiomatous” lesions to large weeping erosions; ocular anomalies that can include microphthalmia, anophthalmia, coloboma, and nasolacrimal duct stenosis/atresia; and facial anomalies that can include ocular hypertelorism or telecanthus, broad nasal tip, upslanted palpebral fissures, cleft lip or prominent philtral pillars that give the appearance of a repaired cleft lip (formerly called "pseudocleft lip") with or without cleft palate, upper lip pits and lower facial weakness (asymmetric crying face or partial 7(th) cranial nerve weakness). Malformed and prominent pinnae and hearing loss from inner ear and/or petrous bone anomalies are common. Intellect is usually normal.
Roberts-SC phocomelia syndrome
MedGen UID:
95931
Concept ID:
C0392475
Congenital Abnormality
Roberts syndrome (RBS) is characterized by prenatal growth retardation (ranging from mild to severe), craniofacial findings (including microcephaly and cleft lip and/or palate) and limb malformations (including bilateral symmetric tetraphocomelia or hypomelia caused by mesomelic shortening). Upper limbs are more severely affected than lower limbs. Other limb malformations include oligodactyly with thumb aplasia or hypoplasia, syndactyly, clinodactyly, and elbow and knee flexion contractures. Craniofacial abnormalities include cleft lip and/or cleft palate, premaxillary prominence, micrognathia, microbrachycephaly, malar flattening, downslanted palpebral fissures, widely spaced eyes, exophthalmos resulting from shallow orbits, corneal clouding, underdeveloped ala nasi, beaked nose, and ear malformations. Intellectual disability is reported in the majority of affected individuals. Mortality is high among severely affected pregnancies and newborns. Mildly affected individuals may survive to adulthood.
Ochoa syndrome
MedGen UID:
98015
Concept ID:
C0403555
Disease or Syndrome
The urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by a severe and early-onset form of dysfunctional urinary voiding. Affected individuals usually present prenatally or in early childhood with grossly distorted renal tracts, comprising dysmorphic bladders and dilatation of the ureter and renal pelvis. They are at high risk of vesicoureteral reflux (VUR), with ascending bacterial infection leading to kidney damage, hypertension, and renal failure. One-third of UFS children also experience constipation or fecal soiling, suggesting that the pathophysiology of the syndrome encompasses a broader functional impairment of elimination. In addition, affected individuals have a characteristic facial grimace when trying to smile (summary by Daly et al., 2010). Genetic Heterogeneity of Urofacial Syndrome Urofacial syndrome-2 (UFS2; 615112) is caused by mutation in the LRIG2 gene (608869) on chromosome 1p13.
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).
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).
Severe X-linked myotubular myopathy
MedGen UID:
98374
Concept ID:
C0410203
Congenital Abnormality
X-linked centronuclear myopathy (XLCNM) (also known as myotubular myopathy [MTM]) is characterized by muscle weakness that ranges from severe to mild. Severe (classic) XLCNM presents prenatally with polyhydramnios and decreased fetal movement and in newborns with weakness, hypotonia and respiratory distress. Affected males have significantly delayed motor milestones and most fail to achieve independent ambulation. Weakness is profound and often involves facial and extraocular muscles. Respiratory failure is nearly uniform, with most affected individuals requiring 24-hour ventilatory assistance. A minority of males with severe XLCNM die in infancy. Males with moderate XLCNM achieve motor milestones more quickly than males with the severe form; about 40% require no ventilator support or intermittent support. Males with mild XLCNM may require ventilatory support only in the newborn period; they have minimally delayed motor milestones, are able to walk, and may lack myopathic facies. The muscle disease of XLCNM is not obviously progressive. Female carriers of XLCNM are generally asymptomatic, although rare manifesting heterozygotes have been described.
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.
Schneckenbecken dysplasia
MedGen UID:
98475
Concept ID:
C0432194
Disease or Syndrome
Boomerang dysplasia
MedGen UID:
96579
Concept ID:
C0432201
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.
Lethal Kniest-like syndrome
MedGen UID:
98144
Concept ID:
C0432208
Congenital Abnormality
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).
Deletion of long arm of chromosome 18
MedGen UID:
96605
Concept ID:
C0432443
Disease or Syndrome
A rare genetic syndrome characterized by the deletion of the long arm of chromosome 18. It is associated with short stature, hypotonia, mental retardation, and hand, foot, skull and facial abnormalities.
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.
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.
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.
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).
Cockayne syndrome, type B
MedGen UID:
155487
Concept ID:
C0751038
Disease or Syndrome
Cockayne syndrome (referred to as CS in this GeneReview) spans a phenotypic spectrum that includes: CS type I, the "classic" or “moderate” form; CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal syndrome (COFS) or Pena-Shokeir syndrome type II; CS type III, a milder form; Xeroderma pigmentosum-Cockayne syndrome (XP-CS). CS type I (moderate CS) is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade. CS type II (severe CS or early-onset CS) is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age seven years. CS type III (mild CS or late-onset CS) is characterized by essentially normal growth and cognitive development or by late onset. Xeroderma pigmentosum-Cockayne syndrome (XP-CS) includes facial freckling and early skin cancers typical of XP and some features typical of CS, including intellectual disability, spasticity, short stature, and hypogonadism. XP-CS does not include skeletal involvement, the facial phenotype of CS, or CNS dysmyelination and calcifications.
Cockayne syndrome type A
MedGen UID:
155488
Concept ID:
C0751039
Disease or Syndrome
Cockayne syndrome (referred to as CS in this GeneReview) spans a phenotypic spectrum that includes: CS type I, the "classic" or “moderate” form; CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal syndrome (COFS) or Pena-Shokeir syndrome type II; CS type III, a milder form; Xeroderma pigmentosum-Cockayne syndrome (XP-CS). CS type I (moderate CS) is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade. CS type II (severe CS or early-onset CS) is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age seven years. CS type III (mild CS or late-onset CS) is characterized by essentially normal growth and cognitive development or by late onset. Xeroderma pigmentosum-Cockayne syndrome (XP-CS) includes facial freckling and early skin cancers typical of XP and some features typical of CS, including intellectual disability, spasticity, short stature, and hypogonadism. XP-CS does not include skeletal involvement, the facial phenotype of CS, or CNS dysmyelination and calcifications.
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.
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.
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.
Pseudoaminopterin syndrome
MedGen UID:
163196
Concept ID:
C0795939
Disease or Syndrome
The pseudoaminopterin syndrome (aminopterin syndrome sine aminopterin; ASSA) is a multiple congenital anomaly disorder characterized by ossification defects of the skull, dysmorphic facial features, delayed development, and variable limb defects. The clinical features resemble the embryopathy caused by maternal treatment with the folic acid antagonist aminopterin, which has been recognized since 1952 (Thiersch, 1952) when aminopterin was used as an abortifacient. The characteristic phenotype of the children who survived infancy after having been exposed to aminopterin or its methyl derivative, methotrexate, in early pregnancy included a very unusual facies, skull anomalies, and skeletal defects (summary by Fraser et al., 1987).
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.
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.
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.
Kabuki make-up syndrome
MedGen UID:
162897
Concept ID:
C0796004
Disease or Syndrome
Kabuki syndrome (KS) is characterized by typical facial features (elongated palpebral fissures with eversion of the lateral third of the lower eyelid; arched and broad eyebrows; short columella with depressed nasal tip; large, prominent, or cupped ears), minor skeletal anomalies, persistence of fetal fingertip pads, mild to moderate intellectual disability, and postnatal growth deficiency. Other findings may include: congenital heart defects, genitourinary anomalies, cleft lip and/or palate, gastrointestinal anomalies including anal atresia, ptosis and strabismus, and widely spaced teeth and hypodontia. Functional differences can include: increased susceptibility to infections and autoimmune disorders, seizures, endocrinologic abnormalities including isolated premature thelarche in females, feeding problems, and hearing loss.
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%.
Lenz microphthalmia syndrome
MedGen UID:
162898
Concept ID:
C0796016
Congenital Abnormality
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.
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.
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.
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
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).
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.
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).
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).
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.
Snyder Robinson syndrome
MedGen UID:
162918
Concept ID:
C0796160
Disease or Syndrome
Snyder-Robinson syndrome (SRS) is an X-linked intellectual disability syndrome characterized by asthenic build, facial dysmorphism with a prominent lower lip, kyphoscoliosis, osteoporosis, and speech abnormalities. Developmental delay usually presents as failure to meet early developmental milestones and then evolves to moderate to profound global intellectual disability (which appears to remain stable over time) and variable motor disability. Asthenic habitus and low muscle mass usually develop during the first year, even in males who are ambulatory. During the first decade, males with SRS develop osteoporosis, resulting in fractures in the absence of trauma.
Toriello Carey syndrome
MedGen UID:
163225
Concept ID:
C0796184
Disease or Syndrome
The Toriello-Carey syndrome is a multiple congenital anomaly disorder with variable systemic manifestations, most commonly including mental retardation, agenesis of the corpus callosum, postnatal growth delay, cardiac defects, usually septal defects, distal limb defects, and urogenital anomalies in affected males. Patients have facial dysmorphic features, micrognathia, including full cheeks, hypertelorism, flattened nasal bridge, anteverted nares, and short neck. Not all features are found in all patients and some patients may have additional features such as anal anomalies or hernias (review by Toriello et al., 2003).
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.
Pashayan syndrome
MedGen UID:
163226
Concept ID:
C0796197
Disease or Syndrome
Telecanthus, displacement of the lacrimal puncta, lacrimal defects, masklike facies, and mental deficiency.
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.
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
X-linked mental retardation syndrome-5 is characterized by 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.
Carnevale syndrome
MedGen UID:
167115
Concept ID:
C0796279
Disease or Syndrome
The term '3MC syndrome' encompasses 4 rare autosomal recessive disorders that were previously designated the Carnevale, Mingarelli, Malpuech, and Michels syndromes, respectively. The main features of these syndromes are facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis, and highly arched eyebrows, which are present in 70% to 95% of cases. Cleft lip and palate, postnatal growth deficiency, cognitive impairment, and hearing loss are also consistent findings, occurring in 40% to 68% of cases. Craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies occur in 20% to 30% of cases. Rare features include anterior chamber defects, cardiac anomalies, caudal appendage, umbilical hernia (omphalocele), and diastasis recti (summary by Rooryck et al., 2011). For a discussion of genetic heterogeneity of 3MC syndrome, see 3MC1 (257920).
Hajdu-Cheney syndrome
MedGen UID:
182961
Concept ID:
C0917715
Congenital Abnormality
Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder characterized by short stature, coarse and dysmorphic facies, bowing of the long bones, and vertebral anomalies. Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. There is progressive focal bone destruction, including acroosteolysis and generalized osteoporosis. Additional and variable features include hearing loss, renal cysts, and cardiovascular anomalies (summary by Ramos et al., 1998; Simpson et al., 2011; Isidor et al., 2011).
McKusick Kaufman syndrome
MedGen UID:
184924
Concept ID:
C0948368
Congenital Abnormality
McKusick-Kaufman syndrome (MKS) is characterized by the triad 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.
Dyskeratosis congenita X-linked
MedGen UID:
216941
Concept ID:
C1148551
Disease or Syndrome
Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. However, the classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Progeroid short stature with pigmented nevi
MedGen UID:
224702
Concept ID:
C1261128
Disease or Syndrome
Mulvihill-Smith syndrome is characterized by premature aging, multiple pigmented nevi, lack of facial subcutaneous fat, microcephaly, short stature, sensorineural hearing loss, and mental retardation. Immunodeficiency may also be a feature. Adult manifestations include the development of tumors, a sleep disorder with severe insomnia, and cognitive decline (summary by Yagihashi et al., 2009).
Carpenter syndrome
MedGen UID:
226897
Concept ID:
C1275078
Disease or Syndrome
Carpenter syndrome is a rare autosomal recessive disorder with the cardinal features of acrocephaly with variable synostosis of the sagittal, lambdoid, and coronal sutures; peculiar facies; brachydactyly of the hands with syndactyly; preaxial polydactyly and syndactyly of the feet; congenital heart defects; growth retardation; mental retardation; hypogenitalism; and obesity. In addition, cerebral malformations, oral and dental abnormalities, coxa valga, genu valgum, hydronephrosis, precocious puberty, and hearing loss may be observed (summary by Altunhan et al., 2011). Genetic Heterogeneity of Carpenter Syndrome Carpenter syndrome-2 (CRPT2; 614976), in which the features of Carpenter syndrome are sometimes associated with defective lateralization, is caused by mutation in the MEGF8 gene (604267).
Pena-Shokeir syndrome type I
MedGen UID:
220903
Concept ID:
C1276035
Disease or Syndrome
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290).
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.
WT limb blood syndrome
MedGen UID:
231231
Concept ID:
C1327917
Disease or Syndrome
Kallmann syndrome 1
MedGen UID:
295872
Concept ID:
C1563719
Disease or Syndrome
Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the setting of hypogonadism. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome [KS]) in approximately 60%. IGD can first be apparent in infancy, adolescence, or adulthood. Infant boys with congenital (i.e., present at birth) IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.
Kallmann syndrome 2
MedGen UID:
289648
Concept ID:
C1563720
Disease or Syndrome
Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the setting of hypogonadism. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome [KS]) in approximately 60%. IGD can first be apparent in infancy, adolescence, or adulthood. Infant boys with congenital (i.e., present at birth) IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.
Megacystis, microcolon, hypoperistalsis syndrome
MedGen UID:
296125
Concept ID:
C1608393
Congenital Abnormality
A rare syndrome characterized by the presence of an enlarged and weak bladder (megacystis), a very small large intestine (microcolon), and weak small intestine that does not function properly (hypoperistalsis). It is caused by a disorder of the smooth muscles of the abdomen and gastrointestinal tract.
Opitz G/BBB syndrome
MedGen UID:
321463
Concept ID:
C1801950
Disease or Syndrome
Features of the Opitz GBBB syndrome include hypertelorism or telecanthus; laryngotracheoesophageal cleft; clefts of lip, palate, and uvula; swallowing difficulty and hoarse cry; genitourinary defects, especially hypospadias in males and splayed labia majora in females; mental retardation; developmental delay; and congenital heart defects. The Opitz GBBB syndrome was earlier thought to be 2 separate X-linked syndromes called the G syndrome and the BBB syndrome; both were listed in the X-linked catalog as recently as the seventh edition of MIM (1986). The Opitz GBBB syndrome is genetically heterogeneous, with both autosomal dominant and X-linked (300000) forms. Robin et al. (1996) compared the phenotypic features of the X-linked and autosomal forms. They found that anteverted nares and posterior pharyngeal cleft were seen only in the X-linked form. However, all other manifestations of the syndrome, such as hypertelorism, swallowing difficulties, hypospadias, and developmental delay, were seen in both forms.
Summitt syndrome
MedGen UID:
369198
Concept ID:
C1802405
Disease or Syndrome
Axenfeld-Rieger syndrome type 2
MedGen UID:
316937
Concept ID:
C1832229
Disease or Syndrome
Axenfeld-Rieger syndrome is an autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, which results in blindness from glaucoma in approximately 50% of affected individuals. Systemic abnormalities are sometimes associated. For a general phenotypic description and a discussion of genetic heterogeneity and nomenclature of Axenfeld-Rieger syndrome, see RIEG1 (180500).
DiGeorge syndrome/velocardiofacial syndrome complex 2
MedGen UID:
321954
Concept ID:
C1832431
Disease or Syndrome
Amelia, autosomal recessive
MedGen UID:
321955
Concept ID:
C1832432
Disease or Syndrome
Microphthalmia syndromic 8
MedGen UID:
330469
Concept ID:
C1832440
Disease or Syndrome
Microphthalmia syndromic 9
MedGen UID:
318679
Concept ID:
C1832661
Disease or Syndrome
Fallot complex with severe mental and growth retardation
MedGen UID:
322025
Concept ID:
C1832735
Disease or Syndrome
Microgastria limb reduction defect
MedGen UID:
322532
Concept ID:
C1834929
Disease or Syndrome
Visceral myopathy
MedGen UID:
331900
Concept ID:
C1835084
Disease or Syndrome
Familial visceral myopathy is a rare inherited form of myopathic pseudoobstruction, characterized by impaired function of enteric smooth muscle cells resulting in abnormal intestinal mobility, severe abdominal pain, malnutrition, and even death (Lehtonen et al., 2012). Visceral myopathy represents a phenotypic spectrum of disease characterized by inter- and intrafamilial variability, in which the most severely affected patients exhibit prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and chronic dependence on total parenteral nutrition (TPN) and urinary catheterization (summary by Wangler et al., 2014). Another form of visceral myopathy with functional gastrointestinal obstruction is associated with external ophthalmoplegia (277320). Functional gastrointestinal obstruction also occurs in association with other abnormalities, such as 'prune belly' syndrome (100100) and Barrett esophagus (Mungan syndrome; 611376). Chronic intestinal pseudoobstruction can also be neuropathic in origin (see 609629).
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.
Holoprosencephaly 9
MedGen UID:
324369
Concept ID:
C1835819
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.
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.
Emanuel syndrome
MedGen UID:
323030
Concept ID:
C1836929
Disease or Syndrome
Emanuel syndrome is characterized by severe intellectual disability, microcephaly, failure to thrive, preauricular tags or pits, ear anomalies, cleft or high-arched palate, micrognathia, kidney abnormalities, congenital heart defects, and genital abnormalities in males.
Meacham syndrome
MedGen UID:
373234
Concept ID:
C1837026
Disease or Syndrome
Sudden infant death with dysgenesis of the testes syndrome
MedGen UID:
332428
Concept ID:
C1837371
Disease or Syndrome
Sudden infant death with dysgenesis of the testes syndrome (SIDDT) is a rare condition that is fatal in the first year of life; its major features include abnormalities of the reproductive system in males, feeding difficulties, and breathing problems. Infants with SIDDT who are genetically male, with one X chromosome and one Y chromosome in each cell, have underdeveloped or abnormal testes. They may also have external genitalia that appear female or that do not look clearly male or clearly female (ambiguous genitalia). In affected infants who are genetically female, with two X chromosomes in each cell, development of the internal and external reproductive organs is normal. SIDDT is associated with abnormal development of the brain, particularly the brainstem, which is the part of the brain that is connected to the spinal cord. The brainstem regulates many basic body functions, including heart rate, breathing, eating, and sleeping. It also relays information about movement and the senses between the brain and the rest of the body. Many features of SIDDT appear to be related to brainstem malfunction, including a slow or uneven heart rate, abnormal breathing patterns, difficulty controlling body temperature, unusual tongue and eye movements, abnormal reflexes, seizures, and feeding difficulties. Affected infants also have an unusual cry that has been described as similar to the bleating of a goat, which is probably a result of abnormal nerve connections between the brain and the voicebox (larynx). The brainstem abnormalities lead to death in the first year of life, when affected infants suddenly stop breathing or their heart stops beating (cardiorespiratory arrest).
Cleft palate, cardiac defect, genital anomalies, and ectrodactyly
MedGen UID:
324947
Concept ID:
C1838121
Disease or Syndrome
Sacral defect with anterior meningocele
MedGen UID:
325455
Concept ID:
C1838568
Disease or Syndrome
Sacral defect with anterior meningocele (SDAM) is a form of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, or meningitis. Inheritance is autosomal dominant (Chatkupt et al., 1994). Welch and Aterman (1984) gave a population frequency of 0.14%. Caudal dysgenesis syndrome and caudal regression syndrome are broad terms that refer to a heterogeneous constellation of congenital caudal anomalies affecting the caudal spine and spinal cord, the hindgut, the urogenital system, and the lower limbs. Approximately 15 to 25% of mothers of children with caudal dysgenesis have insulin-dependent diabetes mellitus (222100) (Lynch et al., 2000). See also Currarino syndrome (176450), a similar disorder caused by mutation in the HLXB9 gene (142994) on chromosome 7q36. Currarino syndrome classically comprises the triad of hemisacrum, anorectal malformation, and presacral mass. However, Currarino syndrome also shows phenotypic variability: Lynch et al. (2000) stated that there is variable expressivity of clinical features and that some patients with Currarino syndrome are asymptomatic. Kochling et al. (2001) found the complete triad of Currarino syndrome in only 8 of 23 patients with mutations in the HLXB9 gene, These reports suggest that some patients previously reported as having forms of sacral agenesis, including SDAM, may have had Currarino syndrome and vice versa. See also spina bifida (182940), which can be seen in some patients with sacral agenesis or caudal regression syndrome and may be etiologically related.
Warburg micro syndrome 1
MedGen UID:
333142
Concept ID:
C1838625
Disease or Syndrome
Puerto rican infant hypotonia syndrome
MedGen UID:
333148
Concept ID:
C1838651
Disease or Syndrome
Widow's peak syndrome
MedGen UID:
374133
Concept ID:
C1839112
Disease or Syndrome
Torticollis keloids cryptorchidism renal dysplasia
MedGen UID:
326819
Concept ID:
C1839129
Disease or Syndrome
SCARF syndrome
MedGen UID:
326461
Concept ID:
C1839321
Disease or Syndrome
TARP syndrome
MedGen UID:
333324
Concept ID:
C1839463
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.
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
46,XY sex reversal 8
MedGen UID:
333416
Concept ID:
C1839840
Disease or Syndrome
Kallmann syndrome with spastic paraplegia
MedGen UID:
333437
Concept ID:
C1839911
Disease or Syndrome
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).
Brachycephalofrontonasal dysplasia
MedGen UID:
326721
Concept ID:
C1840378
Disease or Syndrome
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).
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.
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%).
Caudal duplication anomaly
MedGen UID:
335822
Concept ID:
C1842884
Disease or Syndrome
Craniolenticulosutural dysplasia
MedGen UID:
334671
Concept ID:
C1843042
Disease or Syndrome
Craniolenticulosutural dysplasia is an autosomal recessive disorder characterized by facial dysmorphism, late-closing fontanels, cataract, and skeletal defects (summary by Boyadjiev et al., 2011).
Noonan-like syndrome with loose anagen hair
MedGen UID:
334697
Concept ID:
C1843181
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.
Abruzzo Erickson syndrome
MedGen UID:
375529
Concept ID:
C1844862
Disease or Syndrome
Catel Manzke syndrome
MedGen UID:
375536
Concept ID:
C1844887
Disease or Syndrome
Catel-Manzke syndrome is characterized by the Pierre Robin anomaly, which comprises cleft palate, glossoptosis, and micrognathia, and a unique form of bilateral hyperphalangy in which there is an accessory bone inserted between the second metacarpal and its corresponding proximal phalanx, resulting in radial deviation of the index finger (summary by Manzke et al., 2008).
Branchial arch syndrome X-linked
MedGen UID:
375543
Concept ID:
C1844918
Disease or Syndrome
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.
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.
Holoprosencephaly, ectrodactyly, and bilateral cleft lip/palate
MedGen UID:
335111
Concept ID:
C1845146
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.
X-linked mental retardation, syndromic, Claes-Jensen type
MedGen UID:
335139
Concept ID:
C1845243
Disease or Syndrome
Martin-Probst deafness-mental retardation syndrome
MedGen UID:
375620
Concept ID:
C1845285
Disease or Syndrome
Mental retardation X-linked with cerebellar hypoplasia and distinctive facial appearance
MedGen UID:
336920
Concept ID:
C1845366
Disease or Syndrome
X-linked mental retardation with short stature, hypogonadism and abnormal gait
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).
Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies
MedGen UID:
337364
Concept ID:
C1846009
Disease or Syndrome
IMAGE syndrome is a rare multisystem disorder characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and steroid replacement therapy commenced. Other reported features in this condition include hypercalciuria and/or hypocalcemia, craniosynostosis, cleft palate, and scoliosis (summary by Balasubramanian et al., 2010).
Siderius X-linked mental retardation syndrome
MedGen UID:
337375
Concept ID:
C1846055
Disease or Syndrome
Armfield X-linked mental retardation syndrome
MedGen UID:
375800
Concept ID:
C1846057
Disease or Syndrome
MECP2 duplication syndrome
MedGen UID:
337496
Concept ID:
C1846058
Mental or Behavioral Dysfunction
The MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by infantile hypotonia, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected individuals) and seizures (in ~50%). MECP2 duplication syndrome is 100% penetrant in males. Occasionally females have been described with a MECP2 duplication and related clinical findings, often associated with concomitant X-chromosomal abnormalities that prevent inactivation of the duplicated region. Generalized tonic-clonic seizures are most often observed; atonic seizures and absence seizures have also been described. One third of affected males are never able to walk independently. Almost 50% of affected males die before age 25 years, presumably from complications of recurrent infection and/or neurologic deterioration. In addition to the core features, autistic behaviors and gastrointestinal dysfunction have been observed in several affected boys. Although interfamilial phenotypic variability is observed, severity is usually consistent within families.
Mental retardation X-linked syndromic 7
MedGen UID:
337403
Concept ID:
C1846170
Disease or Syndrome
X-linked lissencephaly 2
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).
Mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity
MedGen UID:
375855
Concept ID:
C1846278
Disease or Syndrome
Cree mental retardation syndrome
MedGen UID:
335673
Concept ID:
C1847361
Disease or Syndrome
Lig4 syndrome
MedGen UID:
339855
Concept ID:
C1847827
Disease or Syndrome
Mental retardation Wolff type
MedGen UID:
336345
Concept ID:
C1848439
Disease or Syndrome
Ulna and fibula absence of with severe limb deficiency
MedGen UID:
336388
Concept ID:
C1848651
Congenital Abnormality
The Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome (AARRS) is a rare autosomal recessive disorder characterized by severe malformations of upper and lower limbs with severely hypoplastic pelvis and abnormal genitalia. The disorder is believed to represent a defect of dorsoventral patterning and outgrowth of limbs (summary by Kantaputra et al., 2010).
Trichomegaly with mental retardation, dwarfism and pigmentary degeneration of retina
MedGen UID:
338532
Concept ID:
C1848745
Congenital Abnormality
Thumb, hypoplastic, with choroid coloboma, poorly developed antihelix, and deafness
MedGen UID:
376448
Concept ID:
C1848816
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).
Robinow syndrome, autosomal recessive
MedGen UID:
341431
Concept ID:
C1849334
Disease or Syndrome
ROR2-related Robinow syndrome is characterized by distinctive craniofacial features, skeletal abnormalities, and other anomalies. Craniofacial features include macrocephaly, broad prominent forehead, low-set ears, ocular hypertelorism, prominent eyes, midface hypoplasia, short upturned nose with depressed nasal bridge and flared nostrils, large and triangular mouth with exposed incisors and upper gums, gum hypertrophy, misaligned teeth, ankyloglossia, and micrognathia. Skeletal abnormalities include short stature with growth retardation, mesomelic or acromesomelic limb shortening, hemivertebrae with fusion of thoracic vertebrae, and brachydactyly. Other common features include micropenis with or without cryptorchidism in males and reduced clitoral size and hypoplasia of the labia majora in females, renal tract abnormalities, and nail hypoplasia or dystrophy. The disorder is recognizable at birth or in early childhood.
Retinitis pigmentosa, deafness, mental retardation, and hypogonadism
MedGen UID:
340317
Concept ID:
C1849401
Disease or Syndrome
Renal dysplasia - limb defects syndrome
MedGen UID:
376585
Concept ID:
C1849438
Disease or Syndrome
Pseudotrisomy 13 syndrome
MedGen UID:
340382
Concept ID:
C1849649
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.
Persistent Mullerian duct syndrome
MedGen UID:
342367
Concept ID:
C1849930
Anatomical Abnormality
The persistent mullerian duct syndrome is characterized by the persistence of mullerian derivatives, uterus and tubes, in otherwise normally virilized males (summary by Knebelmann et al., 1991).
Osteogenesis imperfecta congenita microcephaly and cataracts
MedGen UID:
337988
Concept ID:
C1850184
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).
Omphalocele exstrophy imperforate anus
MedGen UID:
338020
Concept ID:
C1850321
Disease or Syndrome
A rare combination of congenital abnormalities that includes omphalocele, cloacal exstrophy, imperforate anus, and spine abnormalities.
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).
Mosaic variegated aneuploidy syndrome
MedGen UID:
338026
Concept ID:
C1850343
Disease or Syndrome
Mosaic variegated aneuploidy is an autosomal recessive disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues (Hanks et al., 2004). The proportion of aneuploid cells varies but is usually more than 25% and is substantially greater than in normal individuals. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor, and leukemia reported in several cases. See also MVA2 (614114), caused by mutation in the CEP57 gene (607951) on chromosome 11q21.
Native American myopathy
MedGen UID:
340586
Concept ID:
C1850625
Disease or Syndrome
Native American myopathy (NAM) is an autosomal recessive disorder characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia provoked by anesthesia. It was first reported in the Lumbee Indian tribe in North Carolina (summary by Stamm et al., 2008).
Laurin-Sandrow syndrome
MedGen UID:
340697
Concept ID:
C1851100
Disease or Syndrome
Lehman syndrome
MedGen UID:
342070
Concept ID:
C1851710
Disease or Syndrome
Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1
MedGen UID:
343663
Concept ID:
C1851841
Disease or Syndrome
Cutis Gyrata syndrome of Beare and Stevenson
MedGen UID:
377668
Concept ID:
C1852406
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.
Noonan syndrome 4
MedGen UID:
339908
Concept ID:
C1853120
Disease or Syndrome
Noonan syndrome (NS) is characterized by short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, characteristic facies, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one third of affected individuals have mild intellectual disability.
Holoprosencephaly, recurrent infections, and monocytosis
MedGen UID:
343987
Concept ID:
C1853187
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.
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.
Fryns-Aftimos syndrome
MedGen UID:
340016
Concept ID:
C1853623
Disease or Syndrome
Lethal multiple pterygium syndrome
MedGen UID:
381473
Concept ID:
C1854678
Disease or Syndrome
Multiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend. The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth. In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life. Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Individuals with this type have severe arthrogryposis. Lethal multiple pterygium syndrome is associated with abnormalities such as underdevelopment (hypoplasia) of the heart, lung, or brain; twisting of the intestines (intestinal malrotation); kidney abnormalities; an opening in the roof of the mouth (a cleft palate); and an unusually small head size (microcephaly). Affected individuals may also develop a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), a condition called a congenital diaphragmatic hernia. Lethal multiple pterygium syndrome is typically fatal in the second or third trimester of pregnancy.
Say Barber Miller syndrome
MedGen UID:
343258
Concept ID:
C1855078
Disease or Syndrome
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)
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).
Iris coloboma with ptosis, hypertelorism, and mental retardation
MedGen UID:
340943
Concept ID:
C1855722
Disease or Syndrome
Baraitser-Winter syndrome is a rare but well-defined developmental disorder recognized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss (summary by Riviere et al., 2012). Genetic Heterogeneity of Baraitser-Winter Syndrome Baraitser-Winter syndrome-2 (BRWS2; 614583) is caused by heterozygous mutation in the ACTG1 gene (102560) on chromosome 17q25.3.
Hypoparathyroidism retardation dysmorphism syndrome
MedGen UID:
340984
Concept ID:
C1855840
Disease or Syndrome
Al Gazali Hirschsprung syndrome
MedGen UID:
344653
Concept ID:
C1856110
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.
Urioste Martinez-Frias syndrome
MedGen UID:
343489
Concept ID:
C1856159
Disease or Syndrome
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).
Genito palato cardiac syndrome
MedGen UID:
341558
Concept ID:
C1856466
Disease or Syndrome
Saito Kuba Tsuruta syndrome
MedGen UID:
383972
Concept ID:
C1856727
Disease or Syndrome
Faciodigitogenital syndrome, recessive
MedGen UID:
341637
Concept ID:
C1856871
Disease or Syndrome
Eyebrows duplication of, with stretchable skin and syndactyly
MedGen UID:
347327
Concept ID:
C1856896
Disease or Syndrome
Ectodermal dysplasia, hypohidrotic, with hypothyroidism and agenesis of the corpus callosum
MedGen UID:
347363
Concept ID:
C1857053
Disease or Syndrome
Dysmyelination with jaundice
MedGen UID:
346526
Concept ID:
C1857143
Disease or Syndrome
Dandy-Walker malformation with mental retardation, macrocephaly, myopia and brachytelephalangy
MedGen UID:
341752
Concept ID:
C1857352
Disease or Syndrome
Craniosynostosis-mental retardation syndrome of Lin and Gettig
MedGen UID:
341781
Concept ID:
C1857473
Disease or Syndrome
Craniosynostosis with fibular aplasia
MedGen UID:
347468
Concept ID:
C1857492
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
Crane-Heise syndrome
MedGen UID:
387847
Concept ID:
C1857532
Disease or Syndrome
Contractures, congenital, torticollis, and malignant hyperthermia
MedGen UID:
347490
Concept ID:
C1857576
Disease or Syndrome
Orstavik Lindemann Solberg syndrome
MedGen UID:
341804
Concept ID:
C1857587
Disease or Syndrome
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).
Kallmann syndrome 4
MedGen UID:
387893
Concept ID:
C1857720
Disease or Syndrome
Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the setting of hypogonadism. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome [KS]) in approximately 60%. IGD can first be apparent in infancy, adolescence, or adulthood. Infant boys with congenital (i.e., present at birth) IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.
3-methylglutaconic aciduria type V
MedGen UID:
347542
Concept ID:
C1857776
Disease or Syndrome
3-Methylglutaconic aciduria type V is an autosomal recessive disorder characterized by the onset of dilated or noncompaction cardiomyopathy in infancy or early childhood. Many patients die of cardiac failure. Other features include microcytic anemia, growth retardation, mild ataxia, mild muscle weakness, genital anomalies in males, and increased urinary excretion of 3-methylglutaconic acid. Some patients may have optic atrophy or delayed psychomotor development (summary by Davey et al., 2006 and Ojala et al., 2012). For a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950).
Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3
MedGen UID:
347666
Concept ID:
C1858562
Disease or Syndrome
Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome-3 (ECC3) is an autosomal dominant disorder comprising absence of the central parts of the hands and feet, resulting in split-hand/foot malformation, ectodermal dysplasia, and cleft lip with or without cleft palate (summary by Maas et al., 1996). Also see EEC1 (129900), which has been mapped to chromosome 7q11.
Verloove Vanhorick Brubakk syndrome
MedGen UID:
395171
Concept ID:
C1859082
Disease or Syndrome
Peroxisome biogenesis disorder 2A
MedGen UID:
347830
Concept ID:
C1859228
Disease or Syndrome
The peroxisome biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 2 (CG2) have mutations in the PEX5 gene. For information on the history of PBD complementation groups, see 214100.
Cerebellar ataxia ectodermal dysplasia
MedGen UID:
347850
Concept ID:
C1859306
Disease or Syndrome
Bowen-Conradi syndrome
MedGen UID:
349160
Concept ID:
C1859405
Disease or Syndrome
Osteodysplastic primordial dwarfism, type 1
MedGen UID:
347149
Concept ID:
C1859452
Congenital Abnormality
Microcephalic osteodysplastic primordial dwarfism type I is a severe autosomal recessive skeletal dysplasia characterized by dwarfism, microcephaly, and neurologic abnormalities, including mental retardation, brain malformations, and ocular/auditory sensory deficits. Patients often die in early childhood (summary by Pierce and Morse, 2012).
Bird headed dwarfism Montreal type
MedGen UID:
347890
Concept ID:
C1859468
Disease or Syndrome
Beemer Ertbruggen syndrome
MedGen UID:
347174
Concept ID:
C1859526
Disease or Syndrome
Feigenbaum Bergeron Richardson syndrome
MedGen UID:
349198
Concept ID:
C1859596
Disease or Syndrome
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.
Adrenal hypoplasia, congenital, with absent pituitary luteinizing hormone
MedGen UID:
348510
Concept ID:
C1859978
Disease or Syndrome
Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis
MedGen UID:
348008
Concept ID:
C1860042
Disease or Syndrome
Cytochrome P450 oxidoreductase (POR) deficiency is a disorder of steroidogenesis with a phenotypic spectrum ranging from cortisol deficiency at the milder end to classic Antley-Bixler syndrome (ABS) at the severe end. Cortisol deficiency can range from clinically insignificant to life threatening; manifestations can include ambiguous genitalia in both males and females; primary amenorrhea and enlarged cystic ovaries in females; poor masculinization during puberty in males; and maternal virilization during pregnancy with an affected fetus. Manifestations of ABS include craniosynostosis; hydrocephalus; distinctive facies; choanal stenosis or atresia; low-set dysplastic ears with stenotic external auditory canals; skeletal anomalies (radiohumeral synostosis, neonatal fractures, congenital bowing of the long bones, joint contractures, arachnodactyly, clubfeet); renal anomalies (ectopic kidneys, duplication of the kidneys, renal hypoplasia, horseshoe kidney, hydronephrosis); and reduction of cognitive function and developmental delay. In moderate POR deficiency, craniofacial and skeletal anomalies are less severe than in ABS.
Ablepharon macrostomia syndrome
MedGen UID:
395439
Concept ID:
C1860224
Disease or Syndrome
Stratton-Parker syndrome
MedGen UID:
350025
Concept ID:
C1861448
Disease or Syndrome
Sternum, premature obliteration of sutures of
MedGen UID:
396144
Concept ID:
C1861485
Finding
Brachydactyly-nystagmus-cerebellar ataxia
MedGen UID:
350589
Concept ID:
C1862099
Disease or Syndrome
Aniridia absent patella
MedGen UID:
400149
Concept ID:
C1862868
Disease or Syndrome
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.
Acromelic frontonasal dysostosis
MedGen UID:
350933
Concept ID:
C1863616
Disease or Syndrome
Verloes et al. (1992) described a rare variant of frontonasal dysplasia (see FND1, 136760), designated acromelic frontonasal dysplasia (AFND), in which similar craniofacial anomalies are associated with variable central nervous system malformations and limb defects including tibial hypoplasia/aplasia, talipes equinovarus, and preaxial polydactyly of the feet.
Arhinia choanal atresia microphthalmia
MedGen UID:
355084
Concept ID:
C1863878
Disease or Syndrome
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.
Microphthalmia syndromic 5
MedGen UID:
350491
Concept ID:
C1864690
Disease or Syndrome
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).
17q21.31 microdeletion 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.
Brachyphalangy, polydactyly, and tibial aplasia/hypoplasia
MedGen UID:
355340
Concept ID:
C1864965
Disease or Syndrome
Skeletal dysplasia and progressive central nervous system degeneration, lethal
MedGen UID:
400685
Concept ID:
C1865117
Disease or Syndrome
Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities
MedGen UID:
355971
Concept ID:
C1865361
Disease or Syndrome
Short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS) is an autosomal recessive multiple congenital anomaly syndrome with features of a first and second branchial arch syndrome. Craniofacial abnormalities can lead to conductive hearing loss, respiratory insufficiency, and feeding difficulties. Additional features include rhizomelic skeletal anomalies as well as abnormalities of the shoulder and pelvic joints. Affected individuals may also have some features of a neurocristopathy or abnormal mesoderm development, such as urogenital anomalies, that are distinct from other branchial arch syndromes (summary by Parry et al., 2013).
Gracile bone dysplasia
MedGen UID:
356331
Concept ID:
C1865639
Disease or Syndrome
Gracile bone dysplasia is a perinatally lethal condition characterized by gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia (summary by Unger et al., 2013).
Otofacioosseous-gonadal syndrome
MedGen UID:
356416
Concept ID:
C1865988
Disease or Syndrome
Coloboma-obesity-hypogenitalism-mental retardation syndrome
MedGen UID:
400954
Concept ID:
C1866256
Disease or Syndrome
Ehlers-Danlos syndrome, musculocontractural type
MedGen UID:
356497
Concept ID:
C1866294
Disease or Syndrome
The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility (Beighton et al., 1998). The major characteristics of the musculocontractural form of EDS include distinctive craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia, hyperextensible thin skin with easy bruisability and atrophic scarring, wrinkled palms, joint hypermobility, and ocular involvement (summary by Malfait et al., 2010). Genetic Heterogeneity of Musculocontractural Ehlers-Danlos Syndrome Ehlers-Danlos syndrome musculocontractural type 2 (EDSMC2; 615539) is caused by mutation in the DSE gene (605942) on chromosome 6q22.
Preaxial hallucal polydactyly
MedGen UID:
356507
Concept ID:
C1866339
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).
Shprintzen omphalocele syndrome
MedGen UID:
356653
Concept ID:
C1866958
Disease or Syndrome
Simosa cranio facial syndrome
MedGen UID:
356655
Concept ID:
C1866962
Disease or Syndrome
Ulnar-mammary syndrome
MedGen UID:
357886
Concept ID:
C1866994
Congenital Abnormality
The ulnar-mammary syndrome is an autosomal dominant disorder characterized by posterior limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty in males, and genital anomalies (Bamshad et al., 1996).
Polydactyly myopia syndrome
MedGen UID:
357424
Concept ID:
C1868117
Disease or Syndrome
ZELLWEGER SYNDROME 2
MedGen UID:
356968
Concept ID:
C1868416
Disease or Syndrome
Meier-Gorlin syndrome
MedGen UID:
401501
Concept ID:
C1868684
Congenital Abnormality
The Meier-Gorlin syndrome is a rare autosomal recessive disorder characterized by severe intrauterine and postnatal growth retardation, microcephaly, bilateral microtia, and aplasia or hypoplasia of the patellae (summary by Shalev and Hall, 2003). While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal (Bicknell et al., 2011). Genetic Heterogeneity of Meier-Gorlin Syndrome Also see Meier-Gorlin syndrome-2 (613800), caused by mutation in the ORC4 gene (603056) on chromosome 2q22; Meier-Gorlin syndrome-3 (613803), caused by mutation in the ORC6 gene (607213) on chromosome 16q12; Meier-Gorlin syndrome-4 (613804), caused by mutation in the CDT1 gene (605525) on chromosome 16q; and Meier-Gorlin syndrome-5 (613805), caused by mutation in the CDC6 gene (602627) on chromosome 17q21.
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%).
Mental retardation, autosomal dominant 1
MedGen UID:
409857
Concept ID:
C1969562
Disease or Syndrome
Hypertelorism, severe, with midface prominence, myopia, mental retardation, and bone fragility
MedGen UID:
370148
Concept ID:
C1970027
Disease or Syndrome
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.
Mental retardation, X-linked 93
MedGen UID:
410164
Concept ID:
C1970841
Disease or Syndrome
Chromosome 10q26 deletion syndrome
MedGen UID:
436306
Concept ID:
C2674937
Disease or Syndrome
Endocrine-cerebroosteodysplasia
MedGen UID:
390740
Concept ID:
C2675227
Disease or Syndrome
Chromosome 15q26-qter deletion syndrome
MedGen UID:
390804
Concept ID:
C2675463
Disease or Syndrome
Severe congenital neutropenia 4, autosomal recessive
MedGen UID:
436454
Concept ID:
C2675526
Disease or Syndrome
Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood. Approximately 20 percent of people with severe congenital neutropenia develop cancer of the blood-forming tissue (leukemia) or a disease of the blood and bone marrow (myelodysplastic syndrome) during adolescence. Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.
Holoprosencephaly 10
MedGen UID:
382704
Concept ID:
C2675857
Disease or Syndrome
Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family. Nonsyndromic holoprosencephaly can be grouped into four types according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In the most severe forms of nonsyndromic holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe nonsyndromic holoprosencephaly die before birth or soon after. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). The life expectancy of these affected individuals varies depending on the severity of symptoms. People with nonsyndromic holoprosencephaly often have a small head (microcephaly), although they can develop a buildup of fluid in the brain (hydrocephalus) that causes increased head size (macrocephaly). Other features may include an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip), one front tooth (a single maxillary central incisor) instead of two, and a flat nasal bridge. The eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia). Some individuals with nonsyndromic holoprosencephaly have a distinctive pattern of facial features, including a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). In general, the severity of facial features is directly related to the severity of the brain abnormalities. However, individuals with mildly affected facial features can have severe brain abnormalities. Some people do not have apparent structural brain abnormalities but have some of the facial features associated with this condition. These individuals are considered to have a form of the disorder known as microform holoprosencephaly and are typically identified after the birth of a severely affected family member. Most people with nonsyndromic holoprosencephaly have developmental delay and intellectual disability. Affected individuals also frequently have a malfunctioning pituitary gland, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. Most commonly, people with nonsyndromic holoprosencephaly and pituitary dysfunction develop diabetes insipidus, a condition that disrupts the balance between fluid intake and urine excretion. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature, heart rate, and breathing. The sense of smell may be diminished (hyposmia) or completely absent (anosmia) if the part of the brain that processes smells is underdeveloped or missing.
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.
Skeletal defects, genital hypoplasia, and mental retardation
MedGen UID:
382795
Concept ID:
C2676231
Disease or Syndrome
Craniofacioskeletal syndrome
MedGen UID:
394716
Concept ID:
C2678036
Disease or Syndrome
Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 1
MedGen UID:
398105
Concept ID:
C2700431
Disease or Syndrome
A distinct group of inborn defects of complex V (ATP synthase) is represented by the enzyme deficiency due to nuclear genome mutations characterized by a selective inhibition of ATP synthase biogenesis. Biochemically, the patients show a generalized decrease in the content of ATP synthase complex which is less than 30% of normal. Most cases present with neonatal-onset hypotonia, lactic acidosis, hyperammonemia, hypertrophic cardiomyopathy, and 3-methylglutaconic aciduria. Many patients die within a few months or years (summary by Mayr et al., 2010). Genetic Heterogeneity of Mitochondrial Complex V Deficiency Other nuclear types of mitochondrial complex V deficiency include MC5DN2 (614052), caused by mutation in the TMEM70 gene (612418) on chromosome 8q21; MC5DN3 (614053), caused by mutation in the ATP5E gene (606153) on chromosome 20q13; and MC5DN4 (615228), caused by mutation in the ATP5A1 gene (164360) on chromosome 18q. Mutations in the mitochondrial-encoded MTATP6 (516060) and MTATP8 (516070) genes can also cause mitochondrial complex V deficiency (see, e.g., 551500 and 500003).
46,XX sex reversal, type 1
MedGen UID:
411324
Concept ID:
C2748895
Disease or Syndrome
46,XX testicular disorder of sex development (46,XX testicular DSD) is characterized by the presence of a 46,XX karyotype; male external genitalia ranging from normal to ambiguous; two testicles; azoospermia; and absence of Müllerian structures. Approximately 80% of individuals with 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size, but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 20% of individuals with 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency.
Chromosome Xq28 duplication syndrome
MedGen UID:
411727
Concept ID:
C2749007
Disease or Syndrome
Tetraamelia, autosomal recessive
MedGen UID:
411798
Concept ID:
C2749279
Disease or Syndrome
Tetra-amelia syndrome is characterized by the (complete) absence of all four limbs and anomalies involving the cranium and the face (cleft lip/cleft palate, micrognathia, microtia, single naris, choanal atresia, absence of nose); eyes (microphthalmia, microcornea, cataract, coloboma, palpebral fusion); urogenital system (renal agenesis, persistence of cloaca, absence of external genitalia, atresia of vagina); anus (atresia); heart; lungs (hypoplasia/aplasia), skeleton (hypoplasia/absence of pelvic bones, absence of ribs, absence of vertebrae), and central nervous system (agenesis of olfactory nerves, agenesis of optic nerves, agenesis of corpus callosum, hydrocephalus). Affected infants are often stillborn or die shortly after birth.
Tetraamelia with ectodermal dysplasia and lacrimal duct abnormalities
MedGen UID:
413568
Concept ID:
C2749282
Disease or Syndrome
Omodysplasia 2
MedGen UID:
413823
Concept ID:
C2750355
Disease or Syndrome
Omodysplasia-2 (OMOD2) is a rare autosomal dominant skeletal dysplasia characterized by shortened humeri, shortened first metacarpal, and craniofacial dysmorphism. See also OMOD1 (258315).
Waardenburg syndrome type 4C
MedGen UID:
413310
Concept ID:
C2750452
Disease or Syndrome
Waardenburg syndrome type 4 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the eye, deafness, and Hirschsprung disease (review by Read and Newton, 1997). WS type 4C is caused by mutation in the SOX10 gene (602229). WS type 4 is genetically heterogeneous (see WS4A; 277580). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS2 (193510), and WS3 (148820).
Noonan syndrome 6
MedGen UID:
413028
Concept ID:
C2750732
Disease or Syndrome
Noonan syndrome (NS) is characterized by short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, characteristic facies, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one third of affected individuals have mild intellectual disability.
Macrocephaly, alopecia, cutis laxa, and scoliosis
MedGen UID:
416526
Concept ID:
C2751321
Disease or Syndrome
Bifid nose, autosomal dominant
MedGen UID:
414016
Concept ID:
C2751431
Disease or Syndrome
Chromosome 19q13.11 deletion syndrome
MedGen UID:
414432
Concept ID:
C2751651
Disease or Syndrome
Microcephaly, growth retardation, cataract, hearing loss, and unusual appearance
MedGen UID:
416652
Concept ID:
C2751870
Disease or Syndrome
Growth retardation, developmental delay, coarse facies, and early death
MedGen UID:
414158
Concept ID:
C2752001
Disease or Syndrome
Kallmann syndrome 3
MedGen UID:
419286
Concept ID:
C2930927
Disease or Syndrome
Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the setting of hypogonadism. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome [KS]) in approximately 60%. IGD can first be apparent in infancy, adolescence, or adulthood. Infant boys with congenital (i.e., present at birth) IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.
Arthrogryposis multiplex congenita
MedGen UID:
419371
Concept ID:
C2931264
Disease or Syndrome
Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders characterized by congenital nonprogressive joint contractures, with a worldwide incidence of 1 in 3,000 live births. AMC can occur in the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth (summary by Markus et al., 2012). There is also a distal form of arthrogryposis multiplex congenita (see DA1A, 108120) and a lethal congenital form (see LCCS1, 253310).
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
N syndrome
MedGen UID:
424834
Concept ID:
C2936859
Disease or Syndrome
Bardet-Biedl syndrome 4
MedGen UID:
423627
Concept ID:
C2936864
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.
Aarskog syndrome, autosomal dominant
MedGen UID:
460570
Concept ID:
C3149220
Disease or Syndrome
Aarskog syndrome is characterized by short stature and facial, limb, and genital anomalies. One form of the disorder is X-linked (see 305400), but there is also evidence for autosomal dominant and autosomal recessive (227330) inheritance (summary by Grier et al., 1983).
Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B2
MedGen UID:
461766
Concept ID:
C3150416
Disease or Syndrome
MDDGB2 is an autosomal recessive congenital muscular dystrophy associated with mental retardation and mild structural brain abnormalities (Yanagisawa et al., 2007). It is part of a group of similar disorders, collectively known as 'dystroglycanopathies,' resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) (Godfrey et al., 2007). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
Fanconi anemia, complementation group O
MedGen UID:
462003
Concept ID:
C3150653
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include one or more of the following: short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ears (and decreased hearing), heart, gastrointestinal system, central nervous system; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%; the incidence of hematologic malignancies (primarily acute myeloid leukemia) 10%-30%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract) 25%-30%.
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.
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
Hemorrhagic destruction of the brain, subependymal calcification, and cataracts
MedGen UID:
462350
Concept ID:
C3151000
Disease or Syndrome
HDBSCC is an autosomal recessive disorder with a distinctive phenotype comprising hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Affected individuals have a catastrophic neurologic clinical course resulting in death in infancy (summary by Akawi et al., 2013).
Meier-Gorlin syndrome 3
MedGen UID:
462463
Concept ID:
C3151113
Disease or Syndrome
Meier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect. Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age). Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge. Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair. Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems.
Meier-Gorlin syndrome 4
MedGen UID:
462470
Concept ID:
C3151120
Disease or Syndrome
Meier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect. Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age). Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge. Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair. Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems.
Meier-Gorlin syndrome 5
MedGen UID:
462476
Concept ID:
C3151126
Disease or Syndrome
Meier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect. Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age). Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge. Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair. Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems.
Multisystemic smooth muscle dysfunction syndrome
MedGen UID:
462551
Concept ID:
C3151201
Disease or Syndrome
Dyskeratosis congenita, autosomal dominant, 3
MedGen UID:
462795
Concept ID:
C3151445
Disease or Syndrome
Dyskeratosis congenita is an inherited bone marrow failure syndrome classically characterized by the triad of mucosal leukoplakia, nail dysplasia, and abnormal skin pigmentation. Affected individuals have an increased risk of aplastic anemia and malignancy. Less common features include epiphora, premature gray hair, microcephaly, developmental delay, and pulmonary fibrosis, among others. The phenotype is highly variable. All affected individuals have shortened telomeres due to a defect in telomere maintenance (summary by Savage et al., 2008). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DCKA1 (127550).
Fanconi anemia, complementation group D2
MedGen UID:
463627
Concept ID:
C3160738
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include one or more of the following: short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ears (and decreased hearing), heart, gastrointestinal system, central nervous system; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%; the incidence of hematologic malignancies (primarily acute myeloid leukemia) 10%-30%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract) 25%-30%.
Fanconi anemia, complementation group E
MedGen UID:
463628
Concept ID:
C3160739
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include one or more of the following: short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ears (and decreased hearing), heart, gastrointestinal system, central nervous system; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%; the incidence of hematologic malignancies (primarily acute myeloid leukemia) 10%-30%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract) 25%-30%.
OGDEN SYNDROME
MedGen UID:
477078
Concept ID:
C3275447
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).
Mitochondrial encephalo-cardio-myopathy due to TMEM70 deficiency
MedGen UID:
481329
Concept ID:
C3279699
Disease or Syndrome
Warburg micro syndrome 2
MedGen UID:
481844
Concept ID:
C3280214
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).
PYCR1-related De Barsy syndrome
MedGen UID:
482429
Concept ID:
C3280799
Disease or Syndrome
Chromosome 17q12 deletion syndrome
MedGen UID:
482768
Concept ID:
C3281138
Disease or Syndrome
Fanconi anemia, complementation group C
MedGen UID:
483324
Concept ID:
C3468041
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include one or more of the following: short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ears (and decreased hearing), heart, gastrointestinal system, central nervous system; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%; the incidence of hematologic malignancies (primarily acute myeloid leukemia) 10%-30%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract) 25%-30%.
Fanconi anemia, complementation group A
MedGen UID:
483333
Concept ID:
C3469521
Disease or Syndrome
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk of malignancy. Physical abnormalities, present in 60%-75% of affected individuals, include one or more of the following: short stature; abnormal skin pigmentation; malformations of the thumbs, forearms, skeletal system, eyes, kidneys and urinary tract, ears (and decreased hearing), heart, gastrointestinal system, central nervous system; hypogonadism; and developmental delay. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. By age 40 to 50 years, the estimated cumulative incidence of bone marrow failure is 90%; the incidence of hematologic malignancies (primarily acute myeloid leukemia) 10%-30%; and of nonhematologic malignancies (solid tumors, particularly of the head and neck, skin, GI tract, and genital tract) 25%-30%.
HYPOGONADOTROPIC HYPOGONADISM 14 WITH OR WITHOUT ANOSMIA
MedGen UID:
761703
Concept ID:
C3540450
Disease or Syndrome
ACRODYSOSTOSIS 2, WITH OR WITHOUT HORMONE RESISTANCE
MedGen UID:
766164
Concept ID:
C3553250
Disease or Syndrome
HYPERTELORISM AND OTHER FACIAL DYSMORPHISM, BRACHYDACTYLY, GENITAL ABNORMALITIES, MENTAL RETARDATION, AND RECURRENT INFLAMMATORY EPISODES
MedGen UID:
766379
Concept ID:
C3553465
Disease or Syndrome
HYPOGONADOTROPIC HYPOGONADISM 8 WITH OR WITHOUT ANOSMIA
MedGen UID:
766755
Concept ID:
C3553841
Disease or Syndrome
HYPOGONADOTROPIC HYPOGONADISM 11 WITH OR WITHOUT ANOSMIA
MedGen UID:
766758
Concept ID:
C3553844
Disease or Syndrome
HYPOGONADOTROPIC HYPOGONADISM 12 WITH OR WITHOUT ANOSMIA
MedGen UID:
766759
Concept ID:
C3553845
Disease or Syndrome
Methylmalonic acidemia with homocystinuria, type cblJ
MedGen UID:
766829
Concept ID:
C3553915
Disease or Syndrome
HYPOGONADOTROPIC HYPOGONADISM 15 WITH OR WITHOUT ANOSMIA
MedGen UID:
766891
Concept ID:
C3553977
Disease or Syndrome
HYPOGONADOTROPIC HYPOGONADISM 16 WITH OR WITHOUT ANOSMIA
MedGen UID:
766935
Concept ID:
C3554021
Disease or Syndrome
CARPENTER SYNDROME 2
MedGen UID:
767161
Concept ID:
C3554247
Disease or Syndrome
Dysmorphism - conductive hearing loss - heart defect
MedGen UID:
767688
Concept ID:
C3554774
Disease or Syndrome
Ohdo syndrome, Maat-Kievit-Brunner type
MedGen UID:
785805
Concept ID:
C3698541
Disease or Syndrome
Meckel syndrome type 1
MedGen UID:
811346
Concept ID:
C3714506
Disease or Syndrome
Mandibular hypoplasia-deafness-progeroid syndrome
MedGen UID:
811623
Concept ID:
C3715192
Disease or Syndrome
NOONAN SYNDROME 8
MedGen UID:
815563
Concept ID:
C3809233
Disease or Syndrome
Hypotonia-speech impairment-severe cognitive delay syndrome
MedGen UID:
815784
Concept ID:
C3809454
Disease or Syndrome
CHROMOSOME 3q13.31 DELETION SYNDROME
MedGen UID:
815820
Concept ID:
C3809490
Disease or Syndrome
Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome
MedGen UID:
816016
Concept ID:
C3809686
Disease or Syndrome
MICROPHTHALMIA, SYNDROMIC 12
MedGen UID:
816133
Concept ID:
C3809803
Disease or Syndrome
TESTICULAR ANOMALIES WITH OR WITHOUT CONGENITAL HEART DISEASE
MedGen UID:
816188
Concept ID:
C3809858
Disease or Syndrome
VAN MALDERGEM SYNDROME 2
MedGen UID:
816205
Concept ID:
C3809875
Disease or Syndrome
Prader-Willi syndrome due to point mutation
MedGen UID:
816207
Concept ID:
C3809877
Disease or Syndrome
STT3B-CDG
MedGen UID:
816397
Concept ID:
C3810067
Disease or Syndrome
SHORT-RIB THORACIC DYSPLASIA 11 WITH OR WITHOUT POLYDACTYLY
MedGen UID:
816530
Concept ID:
C3810200
Disease or Syndrome
WARBURG MICRO SYNDROME 4
MedGen UID:
816595
Concept ID:
C3810265
Disease or Syndrome
Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency
MedGen UID:
816736
Concept ID:
C3810406
Disease or Syndrome

Recent clinical studies

Etiology

Hougaard KS, Larsen AD, Hannerz H, Andersen AM, Jørgensen KT, Toft GV, Bonde JP, Jensen MS
BMC Urol 2014 Feb 28;14:23. doi: 10.1186/1471-2490-14-23. [Epub ahead of print] PMID: 24581337Free PMC Article
Jørgensen KT, Jensen MS, Toft GV, Larsen AD, Bonde JP, Hougaard KS
Scand J Work Environ Health 2014 May 1;40(3):323-30. Epub 2013 Nov 12 doi: 10.5271/sjweh.3399. [Epub ahead of print] PMID: 24220013
Kvist K, Clasen-Linde E, Cortes D, Petersen BL, Thorup J
J Urol 2014 Apr;191(4):1084-9. Epub 2013 Oct 3 doi: 10.1016/j.juro.2013.10.001. [Epub ahead of print] PMID: 24095908
Gurney J, Sarfati D, Stanley J, Studd R
J Urol 2013 Nov;190(5):1852-7. Epub 2013 May 9 doi: 10.1016/j.juro.2013.05.002. [Epub ahead of print] PMID: 23665269
Zakaria M, Azab S, El baz M, Fawaz L, Bahagat A
J Pediatr Urol 2013 Dec;9(6 Pt A):815-9. Epub 2012 Dec 4 doi: 10.1016/j.jpurol.2012.10.024. [Epub ahead of print] PMID: 23218756

Diagnosis

Kolon TF, Herndon CD, Baker LA, Baskin LS, Baxter CG, Cheng EY, Diaz M, Lee PA, Seashore CJ, Tasian GE, Barthold JS; American Urological Assocation
J Urol 2014 Aug;192(2):337-45. Epub 2014 May 20 doi: 10.1016/j.juro.2014.05.005. [Epub ahead of print] PMID: 24857650
Hougaard KS, Larsen AD, Hannerz H, Andersen AM, Jørgensen KT, Toft GV, Bonde JP, Jensen MS
BMC Urol 2014 Feb 28;14:23. doi: 10.1186/1471-2490-14-23. [Epub ahead of print] PMID: 24581337Free PMC Article
Moslemi MK
J Pediatr Urol 2014 Apr;10(2):230-2. Epub 2013 Sep 15 doi: 10.1016/j.jpurol.2013.08.009. [Epub ahead of print] PMID: 24090631
Christman MS, Zderic SA, Kolon TF
J Urol 2013 Oct;190(4 Suppl):1561-5. Epub 2013 Feb 14 doi: 10.1016/j.juro.2013.02.017. [Epub ahead of print] PMID: 23416638
Zakaria M, Azab S, El baz M, Fawaz L, Bahagat A
J Pediatr Urol 2013 Dec;9(6 Pt A):815-9. Epub 2012 Dec 4 doi: 10.1016/j.jpurol.2012.10.024. [Epub ahead of print] PMID: 23218756

Therapy

Kollin C, Ritzén EM
Pediatr Endocrinol Rev 2014 Feb;11 Suppl 2:240-50. PMID: 24683948
Groheux D, Teyton P, Vercellino L, Ferretti A, Rubello D, Hindié E
Biomed Pharmacother 2013 Jul;67(6):533-8. Epub 2013 May 7 doi: 10.1016/j.biopha.2013.04.011. [Epub ahead of print] PMID: 23721825
Rossi V, Sartori A, Bordin G, Parolini F, Morandi A, Arnoldi R, Brisighelli G, Leva E, Torricelli EM
Minerva Pediatr 2013 Jun;65(3):261-9. PMID: 23685377
Rantakokko P, Main KM, Wohlfart-Veje C, Kiviranta H, Airaksinen R, Vartiainen T, Skakkebæk NE, Toppari J, Virtanen HE
Hum Reprod 2013 Jun;28(6):1647-60. Epub 2013 Mar 21 doi: 10.1093/humrep/det040. [Epub ahead of print] PMID: 23520400
Zakaria M, Azab S, El baz M, Fawaz L, Bahagat A
J Pediatr Urol 2013 Dec;9(6 Pt A):815-9. Epub 2012 Dec 4 doi: 10.1016/j.jpurol.2012.10.024. [Epub ahead of print] PMID: 23218756

Prognosis

Hougaard KS, Larsen AD, Hannerz H, Andersen AM, Jørgensen KT, Toft GV, Bonde JP, Jensen MS
BMC Urol 2014 Feb 28;14:23. doi: 10.1186/1471-2490-14-23. [Epub ahead of print] PMID: 24581337Free PMC Article
Moslemi MK
J Pediatr Urol 2014 Apr;10(2):230-2. Epub 2013 Sep 15 doi: 10.1016/j.jpurol.2013.08.009. [Epub ahead of print] PMID: 24090631
Gurney J, Sarfati D, Stanley J, Studd R
J Urol 2013 Nov;190(5):1852-7. Epub 2013 May 9 doi: 10.1016/j.juro.2013.05.002. [Epub ahead of print] PMID: 23665269
Christman MS, Zderic SA, Kolon TF
J Urol 2013 Oct;190(4 Suppl):1561-5. Epub 2013 Feb 14 doi: 10.1016/j.juro.2013.02.017. [Epub ahead of print] PMID: 23416638
Zakaria M, Azab S, El baz M, Fawaz L, Bahagat A
J Pediatr Urol 2013 Dec;9(6 Pt A):815-9. Epub 2012 Dec 4 doi: 10.1016/j.jpurol.2012.10.024. [Epub ahead of print] PMID: 23218756

Clinical prediction guides

Koni A, Ozseker HS, Arpali E, Kilinc E, Dogan HS, Akyol A, Tekgul S
J Urol 2014 Oct;192(4):1183-8. Epub 2014 May 17 doi: 10.1016/j.juro.2014.05.048. [Epub ahead of print] PMID: 24840535
Thankamony A, Lek N, Carroll D, Williams M, Dunger DB, Acerini CL, Ong KK, Hughes IA
Environ Health Perspect 2014 Feb;122(2):207-11. Epub 2013 Dec 6 doi: 10.1289/ehp.1307178. [Epub ahead of print] PMID: 24316680Free PMC Article
Vesterholm Jensen D, Christensen J, Virtanen HE, Skakkebæk NE, Main KM, Toppari J, Veje CW, Andersson AM, Nielsen F, Grandjean P, Jensen TK
Reproduction 2014;147(4):411-7. Epub 2014 Mar 2 doi: 10.1530/REP-13-0444. PMID: 24218628
Gurney J, Sarfati D, Stanley J, Studd R
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