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Sensorineural hearing loss

MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
Synonyms: Hearing Loss, Sensorineural; Sensorineural Hearing Loss
SNOMED CT: Sensorineural hearing loss (60700002); Sensorineural deafness (60700002); Neurosensory deafness (60700002); Perceptive hearing loss (60700002); Perceptive deafness (60700002); SND - Sensorineural deafness (60700002); Sensory-neural deafness (60700002); Sensory-neural hearing loss (60700002); SNHL - Sensorineural hearing loss (60700002); PD - Perceptive deafness (60700002)
 

Definition

Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM. [from MeSH]

Conditions with this feature

Progressive myositis ossificans
MedGen UID:
4698
Concept ID:
C0016037
Disease or Syndrome
Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner, with most patients being confined to a wheelchair by the third decade of life and requiring lifelong care (summary by Petrie et al., 2009).
Von Hippel-Lindau syndrome
MedGen UID:
42458
Concept ID:
C0019562
Disease or Syndrome
Von Hippel-Lindau (VHL) syndrome is characterized by hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear cell renal cell carcinoma; pheochromocytoma, pancreatic cysts, and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts. Cerebellar hemangioblastomas may be associated with headache, vomiting, gait disturbances, or ataxia. Spinal hemangioblastomas and related syrinx usually present with pain. Sensory and motor loss may develop with cord compression. Retinal hemangioblastomas may be the initial manifestation of VHL syndrome and can cause vision loss. Renal cell carcinoma occurs in about 70% of individuals with VHL and is the leading cause of mortality. Pheochromocytomas can be asymptomatic but may cause sustained or episodic hypertension. Pancreatic lesions often remain asymptomatic and rarely cause endocrine or exocrine insufficiency. Endolymphatic sac tumors can cause hearing loss of varying severity, which can be a presenting symptom. Cystadenomas of the epididymis are relatively common. They rarely cause problems, unless bilateral, in which case they may result in infertility.
Neuropathy hereditary sensory and autonomic type 1
MedGen UID:
5645
Concept ID:
C0020071
Disease or Syndrome
Hereditary sensory neuropathy type IA (HSN1A) is an axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena including dysesthesia and characteristic "lightning" or "shooting" pains. Loss of sensation can lead to painless injuries, which, if unrecognized, result in slow wound healing and subsequent osteomyelitis requiring distal amputations. HSN1A is often associated with progressive sensorineural deafness. Motor involvement is present in all advanced cases and can be severe. After age 20 years, the distal wasting and weakness may involve proximal muscles so that a person in his/her 60s or 70s may require a wheelchair for mobility. Drenching sweating of the hands and feet is sometimes reported and occasionally pupillary abnormalities are observed; however, visceral signs of autonomic involvement are rare.
Kearns Sayre syndrome
MedGen UID:
9618
Concept ID:
C0022541
Disease or Syndrome
A mitochondrial disorder featuring the triad of chronic progressive EXTERNAL OPHTHALMOPLEGIA, cardiomyopathy (CARDIOMYOPATHIES) with conduction block (HEART BLOCK), and RETINITIS PIGMENTOSA. Disease onset is in the first or second decade. Elevated CSF protein, sensorineural deafness, seizures, and pyramidal signs may also be present. Ragged-red fibers are found on muscle biopsy. (Adams et al., Principles of Neurology, 6th ed, p984)
Leigh syndrome
MedGen UID:
44095
Concept ID:
C0023264
Disease or Syndrome
Leigh syndrome is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation (Dahl, 1998). Leigh syndrome may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes: complex I deficiency (252010), complex II deficiency (252011), complex III deficiency (124000), complex IV deficiency (cytochrome c oxidase; 220110), or complex V deficiency (604273).
Deficiency of alpha-mannosidase
MedGen UID:
7467
Concept ID:
C0024748
Disease or Syndrome
Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. Three clinical subtypes include: A mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression (type 1); A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression (type 2); and A severe form manifested as prenatal loss or early death from progressive central nervous system involvement (type 3). Individuals with a milder phenotype have mild-to-moderate intellectual disability, impaired hearing, characteristic coarse features, clinical or radiographic skeletal abnormalities, immunodeficiency, and primary central nervous system disease, mainly cerebellar involvement causing ataxia. Periods of psychiatric symptoms are common. Associated medical problems can include corneal opacities, hepatosplenomegaly, aseptic destructive arthritis, and metabolic myopathy. Alpha-mannosidosis is insidiously progressive; some individuals may live into the sixth decade.
Nail-patella syndrome
MedGen UID:
10257
Concept ID:
C0027341
Congenital Abnormality
Nail-patella syndrome (NPS) involves a classic clinical tetrad of changes in the nails, knees, and elbows, and the presence of iliac horns. Nail changes are the most constant feature of NPS. Nails may be absent, hypoplastic, or dystrophic; ridged longitudinally or horizontally; pitted; discolored; separated into two halves by a longitudinal cleft or ridge of skin; and thin or (less often) thickened. The patellae may be small, irregularly shaped, or absent. Elbow abnormalities may include limitation of extension, pronation, and supination; cubitus valgus; and antecubital pterygia. Iliac horns are bilateral, conical, bony processes that project posteriorly and laterally from the central part of the iliac bones of the pelvis. Renal involvement, first manifest as proteinuria with or without hematuria, occurs in 30%-50% of affected individuals; end-stage renal disease (ESRD) occurs in about 5% of affected individuals. Primary open-angle glaucoma and ocular hypertension occur at increased frequency and at a younger age than in the general population.
Phytanic acid storage disease
MedGen UID:
11161
Concept ID:
C0034960
Disease or Syndrome
Refsum disease is characterized by anosmia and early-onset retinitis pigmentosa, which are both universal findings with variable combinations of neuropathy, deafness, ataxia, and ichthyosis. Onset of symptoms ranges from age seven months to older than age 50 years. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems which develop later in life.
Noonan syndrome 1
MedGen UID:
22527
Concept ID:
C0041409
Disease or Syndrome
Noonan syndrome (NS) is characterized by characteristic facies, 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, 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 fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.
Diabetes mellitus AND insipidus with optic atrophy AND deafness
MedGen UID:
21923
Concept ID:
C0043207
Disease or Syndrome
WFS1-related disorders range from Wolfram syndrome (WFS) to WFS1-related low-frequency sensory hearing loss (also known as DFNA6/14/38 low-frequency sensorineural hearing loss [LFSNHL]). WFS is a progressive neurodegenerative disorder characterized by onset of diabetes mellitus and optic atrophy before age 16 years, and typically associated with sensorineural hearing loss, progressive neurologic abnormalities (cerebellar ataxia, peripheral neuropathy, dementia, psychiatric illness, and urinary tract atony), and other endocrine abnormalities. Median age at death is 30 years. WFS-like disease is characterized by sensorineural hearing loss, diabetes mellitus, psychiatric illness, and variable optic atrophy. WFS1-related LFSNHL is characterized by congenital, nonsyndromic, slowly progressive, low-frequency (<2000 Hz) sensorineural hearing loss.
Zellweger syndrome
MedGen UID:
21958
Concept ID:
C0043459
Congenital Abnormality
Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD, ZSS) is a continuum comprising 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.
Myoclonus with epilepsy with ragged red fibers
MedGen UID:
56486
Concept ID:
C0162672
Disease or Syndrome
A very rare mitochondrial abnormality characterized by myoclonic epilepsy and the microscopic finding of ragged-red fibers in muscle tissues.
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).
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.
Noonan syndrome with multiple lentigines
MedGen UID:
104494
Concept ID:
C0175704
Disease or Syndrome
Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features, including widely spaced eyes and ptosis. 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 NSML 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, although most affected individuals have a height that is less than the 25(th) percentile for age. Sensorineural hearing deficits, present in approximately 20%, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML.
Cerebro-oculo-facio-skeletal syndrome
MedGen UID:
66320
Concept ID:
C0220722
Congenital Abnormality
Cerebrooculofacioskeletal syndrome is an autosomal recessive progressive neurodegenerative disorder characterized by microcephaly, congenital cataracts, severe mental retardation, facial dysmorphism, and arthrogryposis (summary by Jaakkola et al., 2010). Genetic Heterogeneity of Cerebrooculofacioskeletal Syndrome See also COFS2 (610756), caused by mutation in the ERCC2 gene (126340); COFS3 (616570), caused by mutation in the ERCC5 gene (133530); and COFS4 (610758), caused by mutation in the ERCC1 gene (126380).
Biotinidase deficiency
MedGen UID:
66323
Concept ID:
C0220754
Disease or Syndrome
If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress.
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), Lujan syndrome (LS), and X-linked Ohdo syndrome. 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, prominent nasal bridge, high narrow palate, and short philtrum. Carrier females in families with FGS1 and LS are typically unaffected. X-linked Ohdo syndrome (XLOS) is characterized by intellectual disability, blepharophimosis, and facial coarsening. A number of individuals with nonsyndromic intellectual disability – including some affected females – have been described.
Facioscapulohumeral muscular dystrophy
MedGen UID:
65956
Concept ID:
C0238288
Disease or Syndrome
Facioscapulohumeral muscular dystrophy (FSHD) typically presents before age 20 years with weakness of the facial muscles and the stabilizers of the scapula or the dorsiflexors of the foot. Severity is highly variable. Weakness is slowly progressive and approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened.
DE SANCTIS-CACCHIONE SYNDROME
MedGen UID:
75550
Concept ID:
C0265201
Congenital Abnormality
A rare autosomal recessive inherited syndrome. It is characterized by xeroderma pigmentosum, mental retardation, dwarfism, hypogonadism, and neurologic abnormalities.
Marshall syndrome
MedGen UID:
82694
Concept ID:
C0265235
Congenital Abnormality
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.Many people with Stickler syndrome have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.
Goldenhar syndrome
MedGen UID:
75554
Concept ID:
C0265240
Congenital Abnormality
Craniofacial microsomia (CFM) includes a spectrum of malformations primarily involving structures derived from the first and second branchial arches. Characteristic findings include facial asymmetry resulting from maxillary and/or mandibular hypoplasia; preauricular or facial tags; ear malformations that can include microtia (hypoplasia of the external ear), anotia (absence of the external ear), or aural atresia (absence of the external ear canal); and hearing loss. Severity can range from subtle facial asymmetry with a small skin tag in front of an otherwise normal-appearing ear to bilateral involvement (typically asymmetric), microtia/anotia with atresia of the ear canals, microphthalmia, and respiratory compromise from severe mandibular hypoplasia. Other craniofacial malformations including cleft lip and/or palate can be seen. Non-craniofacial malformations, especially vertebral, renal, cardiac, and limb, can be seen.
Townes syndrome
MedGen UID:
75555
Concept ID:
C0265246
Disease or Syndrome
Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (84%), dysplastic ears (87%; 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 (42%), including end-stage renal disease (ESRD), 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 individuals. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation.
Coffin-Lowry syndrome
MedGen UID:
75556
Concept ID:
C0265252
Disease or Syndrome
Coffin-Lowry syndrome (CLS) is usually characterized by severe-to-profound intellectual disability in males; less severely impaired individuals have been reported. Intellect ranges from normal to profoundly impaired in heterozygous females. The facial appearance is characteristic in the affected, older male child or adult. The hands are short, soft, and fleshy, often with remarkably hyperextensible fingers that taper from wide (proximally) to narrow with small terminal phalanges and nails. Males are consistently below the third centile in height. Microcephaly is common. Cardiac abnormalities may be present and can contribute to premature death. Stimulus-induced drop attacks (SIDAs) in which unexpected tactile or auditory stimuli or excitement triggers a brief collapse but no loss of consciousness are present in approximately 20% of affected individuals. Typically SIDAs begin between mid-childhood and the teens. Progressive kyphoscoliosis is one of the most difficult aspects of long-term care. Life span may be reduced.
Frontometaphyseal dysplasia
MedGen UID:
82703
Concept ID:
C0265293
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.
Pili torti-deafness syndrome
MedGen UID:
82728
Concept ID:
C0266006
Congenital Abnormality
Bjornstad syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and pili torti. The hearing loss is congenital and of variable severity. Pili torti (twisted hairs), a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair very brittle, is usually recognized early in childhood (Selvaag, 2000).
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.
Xeroderma pigmentosum, type 1
MedGen UID:
82775
Concept ID:
C0268135
Congenital Abnormality
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
Xeroderma pigmentosum, group D
MedGen UID:
75656
Concept ID:
C0268138
Congenital Abnormality
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
Sialidosis, type II
MedGen UID:
120621
Concept ID:
C0268226
Disease or Syndrome
Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (604369) is a form of 'free' sialic acid disease. Classification Lowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.
Cytochrome-c oxidase deficiency
MedGen UID:
75662
Concept ID:
C0268237
Congenital Abnormality
Complex IV (cytochrome c oxidase; EC 1.9.3.1) is the terminal enzyme of the respiratory chain and consists of 13 polypeptide subunits, 3 of which are encoded by mitochondrial DNA. The 3 mitochondrially encoded proteins in the cytochrome oxidase complex are the actual catalytic subunits that carry out the electron transport function (Saraste, 1983). See 123995 for discussion of some of the nuclear-encoded subunits. Shoubridge (2001) provided a comprehensive review of cytochrome c oxidase deficiency and noted that most isolated COX deficiencies are inherited as autosomal recessive disorders caused by mutations in nuclear-encoded genes; mutations in the mtDNA-encoded COX subunit genes are relatively rare.
Triglyceride storage disease with ichthyosis
MedGen UID:
82780
Concept ID:
C0268238
Disease or Syndrome
Chanarin-Dorfman syndrome is a condition in which fats (lipids) are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides, and these fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. People with this condition also have dry, scaly skin (ichthyosis), which is usually present at birth. Additional features of this condition include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts), difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness (myopathy), involuntary movement of the eyes (nystagmus), and mild intellectual disability.The signs and symptoms vary greatly among individuals with Chanarin-Dorfman syndrome. Some people may have ichthyosis only, while others may have problems affecting many areas of the body.
Hyperphosphatasemia with bone disease
MedGen UID:
75678
Concept ID:
C0268414
Disease or Syndrome
Paget disease of bone-5 is an autosomal recessive, juvenile-onset form of Paget disease, a disorder of the skeleton resulting from abnormal bone resorption and formation. Clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness. There is phenotypic variability, with some patients presenting in infancy, while others present later in childhood (summary by Naot et al., 2014). For discussion of genetic heterogeneity of Paget disease of bone, see 167250.
Hyperleucine-isoleucinemia
MedGen UID:
82821
Concept ID:
C0268574
Congenital Abnormality
Histidine transport defect
MedGen UID:
82825
Concept ID:
C0268642
Congenital Abnormality
An increased concentration of histidine in the urine.
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, highly arched eyebrows, long eyelashes, short nose with anteverted nares, 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.
Infantile Refsum disease
MedGen UID:
79470
Concept ID:
C0282527
Disease or Syndrome
Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD, ZSS) is a continuum comprising 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.
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.
Hypogonadism, diabetes mellitus, alopecia, mental retardation and electrocardiographic abnormalities
MedGen UID:
83337
Concept ID:
C0342286
Congenital Abnormality
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. Ten types and their associated genes are recognized. The age of onset ranges from infancy to late adulthood; the rate of progression varies. Cognitive decline occurs in some subtypes, but more often cognition is relatively spared. Cerebellar atrophy is a frequent finding in some subtypes.
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.
Diabetes-deafness syndrome maternally transmitted
MedGen UID:
90979
Concept ID:
C0342289
Congenital Abnormality
Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations.
Autosomal recessive hypophosphatemic vitamin D refractory rickets
MedGen UID:
137975
Concept ID:
C0342643
Disease or Syndrome
Hereditary hypophosphatemic rickets is a disorder related to low levels of phosphate in the blood (hypophosphatemia). Phosphate is a mineral that is essential for the normal formation of bones and teeth.In most cases, the signs and symptoms of hereditary hypophosphatemic rickets begin in early childhood. The features of the disorder vary widely, even among affected members of the same family. Mildly affected individuals may have hypophosphatemia without other signs and symptoms. More severely affected children experience slow growth and are shorter than their peers. They develop bone abnormalities that can interfere with movement and cause bone pain. The most noticeable of these abnormalities are bowed legs or knock knees (a condition in which the lower legs are positioned at an outward angle). These abnormalities become apparent with weight-bearing activities such as walking. If untreated, they tend to worsen with time.Other signs and symptoms of hereditary hypophosphatemic rickets can include premature fusion of the skull bones (craniosynostosis) and dental abnormalities. The disorder may also cause abnormal bone growth where ligaments and tendons attach to joints (enthesopathy). In adults, hypophosphatemia is characterized by a softening of the bones known as osteomalacia.Researchers have described several forms of hereditary hypophosphatemic rickets, which are distinguished by their pattern of inheritance and genetic cause. The most common form of the disorder is known as X-linked hypophosphatemic rickets (XLH). It has an X-linked dominant pattern of inheritance. X-linked recessive, autosomal dominant, and autosomal recessive forms of the disorder are much rarer.Another rare type of the disorder is known as hereditary hypophosphatemic rickets with hypercalciuria (HHRH). In addition to hypophosphatemia, this condition is characterized by the excretion of high levels of calcium in the urine (hypercalciuria).
Klein-Waardenberg syndrome
MedGen UID:
449531
Concept ID:
C0342680
Disease or Syndrome
Waardenburg syndrome type 3 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; presence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi; and upper limb abnormalities (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 3 is also referred to as 'Klein-Waardenburg syndrome' (Gorlin et al., 1976). Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type IV (WS4; 277580), also known as Waardenburg-Shah syndrome, has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010).
Carbohydrate-deficient glycoprotein syndrome type II
MedGen UID:
87610
Concept ID:
C0349654
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. These glycoconjugates play critical roles in metabolism, cell recognition and adhesion, cell migration, protease resistance, host defense, and antigenicity, among others. CDGs are divided into 2 main groups: type I CDGs (see, e.g., CDG1A, 212065) comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs refer to defects in the trimming and processing of the protein-bound glycans either late in the endoplasmic reticulum or the Golgi compartments. The biochemical changes of CDGs are most readily observed in serum transferrin (TF; 190000), and the diagnosis is usually made by isoelectric focusing of this glycoprotein (reviews by Marquardt and Denecke, 2003; Grunewald et al., 2002). Genetic Heterogeneity of Congenital Disorder of Glycosylation Type II Multiple forms of CDG type II have been identified; see CDG2B (606056) through CDG2P (616829).
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.
X-linked hereditary motor and sensory neuropathy
MedGen UID:
98290
Concept ID:
C0393808
Disease or Syndrome
Charcot-Marie-Tooth neuropathy X type 1 (CMTX1) is characterized by a moderate to severe motor and sensory neuropathy in affected males and usually mild to no symptoms in carrier females. Sensorineural deafness and central nervous system symptoms also occur in some families.
Prune belly syndrome with pulmonic stenosis, mental retardation and deafness
MedGen UID:
96043
Concept ID:
C0403551
Disease or Syndrome
Renal tubular acidosis with progressive nerve deafness
MedGen UID:
98336
Concept ID:
C0403554
Disease or Syndrome
Renal tubular acidosis with deafness is a disorder characterized by kidney (renal) problems and hearing loss. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with this disorder, the kidneys do not remove enough acidic compounds from the body. Instead, the acids are absorbed back into the bloodstream, and the blood becomes too acidic. This chemical imbalance, called metabolic acidosis, can result in a range of signs and symptoms that vary in severity. Metabolic acidosis often causes nausea, vomiting, and dehydration; affected infants tend to have problems feeding and gaining weight (failure to thrive). Most children and adults with renal tubular acidosis with deafness have short stature, and many develop kidney stones.The metabolic acidosis that occurs in renal tubular acidosis with deafness may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. Rarely, people with renal tubular acidosis with deafness have episodes of hypokalemic paralysis, a condition that causes extreme muscle weakness associated with low levels of potassium in the blood (hypokalemia).In people with renal tubular acidosis with deafness, hearing loss caused by changes in the inner ear (sensorineural hearing loss) usually begins between childhood and young adulthood, and gradually gets worse. An inner ear abnormality affecting both ears occurs in most people with this disorder. This feature, which is called enlarged vestibular aqueduct, can be seen with medical imaging. The vestibular aqueduct is a bony canal that runs from the inner ear into the temporal bone of the skull and toward the brain. The relationship between enlarged vestibular aqueduct and hearing loss is unclear. In renal tubular acidosis with deafness, enlarged vestibular aqueduct typically occurs in individuals whose hearing loss begins in childhood.
Familial cutaneous collagenoma
MedGen UID:
96073
Concept ID:
C0406817
Neoplastic Process
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).
Worth disease
MedGen UID:
140932
Concept ID:
C0432273
Disease or Syndrome
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.
Gonadal dysgenesis with auditory dysfunction, autosomal recessive inheritance
MedGen UID:
151934
Concept ID:
C0685838
Congenital Abnormality
Perrault syndrome is a sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement (summary by Pierce et al., 2010). Pierce et al. (2010) noted that clinical heterogeneity of Perrault syndrome has prompted classification into type I, which is static and without neurologic disease, and type II, which is with progressive neurologic disease. Genetic Heterogeneity of Perrault Syndrome See also PRLTS2 (614926), caused by mutation in the HARS2 gene (600783) on chromosome 5q31; PRLTS3 (614129), caused by mutation in the CLPP gene (601119) on chromosome 19p13; PRLTS4 (615300), caused by mutation in the LARS2 gene (604544) on chromosome 3p21; and PRLTS5 (616138), caused by mutation in the C10ORF2 gene (606075) on chromosome 10q24.
Cockayne syndrome 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.
UDPglucose-4-epimerase deficiency
MedGen UID:
199598
Concept ID:
C0751161
Disease or Syndrome
Epimerase deficiency galactosemia (GALE deficiency galactosemia) is a continuum comprising three forms: Generalized. Enzyme activity is profoundly decreased in all tissues tested. Peripheral. Enzyme activity is deficient in red blood cells (RBC) and circulating white blood cells, but normal or near normal in all other tissues. Intermediate. Enzyme activity is deficient in red blood cells and circulating white blood cells and less than 50% of normal levels in other cells tested. Infants with generalized epimerase deficiency galactosemia develop clinical findings on a regular milk diet (which contains lactose, a disaccharide of galactose and glucose); manifestations include hypotonia, poor feeding, vomiting, weight loss, jaundice, hepatomegaly, liver dysfunction, aminoaciduria, and cataracts. Prompt removal of galactose/lactose from their diet resolves or prevents these acute symptoms. In contrast, neonates with the peripheral or intermediate form generally remain clinically well even on a regular milk diet and are usually only identified by biochemical testing, often in newborn screening programs.
Cowchock syndrome
MedGen UID:
162891
Concept ID:
C0795910
Disease or Syndrome
Charcot-Marie-Tooth (CMT) hereditary neuropathy refers to a group of disorders characterized by a chronic motor and sensory polyneuropathy. The affected individual typically has distal muscle weakness and atrophy often associated with mild to moderate sensory loss, depressed tendon reflexes, and high-arched feet.
Fountain syndrome
MedGen UID:
208650
Concept ID:
C0795944
Disease or Syndrome
Coarse facies, mental retardation, hearing loss, and skeletal abnormalities are the major symptoms.
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.
Richards-Rundle syndrome
MedGen UID:
163219
Concept ID:
C0796136
Disease or Syndrome
An extremely rare neurodegenerative disorder characterized by progressive spinocerebellar ataxia, sensorineural hearing loss, and hypergonadotropic hypogonadism associated with additional neurological manifestations (such as peripheral muscle wasting, nystagmus, intellectual disability or dementia) and ketoaciduria.
Spondyloperipheral dysplasia
MedGen UID:
163223
Concept ID:
C0796173
Disease or Syndrome
Spondyloperipheral dysplasia is a disorder that impairs bone growth. This condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly), with the exception of the first (big) toes. Other skeletal abnormalities associated with spondyloperipheral dysplasia include short stature, shortened long bones of the arms and legs, exaggerated curvature of the lower back (lordosis), and an inward- and upward-turning foot (clubfoot). Additionally, some affected individuals have nearsightedness (myopia), hearing loss, and intellectual disability.
Pettigrew syndrome
MedGen UID:
162924
Concept ID:
C0796254
Disease or Syndrome
Pettigrew syndrome is characterized by mental retardation and highly variable additional features, including choreoathetosis, hydrocephalus, Dandy-Walker malformation, seizures, and iron or calcium deposition in the brain, both between and within families (summary by Cacciagli et al., 2014). See 311510 for another X-linked mental retardation syndrome associated with basal ganglia disease (Waisman syndrome). See 220219 for another mental retardation syndrome with Dandy-Walker malformation.
Brown-Vialetto-Van Laere syndrome
MedGen UID:
163239
Concept ID:
C0796274
Disease or Syndrome
Riboflavin transporter deficiency neuronopathy is a disorder that affects nerve cells (neurons). Affected individuals typically have hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and signs of damage to other nerves.In addition to nerves in the inner ear, riboflavin transporter deficiency neuronopathy involves nerves found in the part of the brain that is connected to the spinal cord (the brainstem), specifically in a region of the brainstem known as the pontobulbar region. Damage to these nerves causes paralysis of the muscles controlled by them, a condition called pontobulbar palsy. Nerves in the pontobulbar region help control several voluntary muscle activities, including breathing, speaking, and moving the limbs. As a result of pontobulbar palsy, people with riboflavin transporter deficiency neuronopathy can have breathing problems; slurred speech; and muscle weakness in the face, neck, shoulders, and limbs. Affected individuals can also have muscle stiffness (spasticity) and exaggerated reflexes.The age at which riboflavin transporter deficiency neuronopathy begins varies from infancy to young adulthood. When the condition begins in infancy, the first symptom is often breathing problems caused by nerve damage, which can be life-threatening. When the condition begins in children or young adults, sensorineural hearing loss usually occurs first, followed by signs of pontobulbar palsy.If not treated, the signs and symptoms of riboflavin transporter deficiency neuronopathy worsen over time. Severe breathing problems and respiratory infections are the usual cause of death in people with this condition. Without treatment, affected infants typically survive less than one year. However, those who develop the condition after age 4 often survive more than 10 years.Riboflavin transporter deficiency neuronopathy encompasses two conditions that were once considered distinct disorders: Brown-Vialetto-Van Laere syndrome (BVVLS) and Fazio-Londe disease. The two conditions have similar signs and symptoms, but Fazio-Londe disease does not include sensorineural hearing loss. Because these two conditions share a genetic cause and have overlapping features, researchers determined that they are forms of a single disorder.
Mitochondrial DNA depletion syndrome 1 (MNGIE type)
MedGen UID:
167876
Concept ID:
C0872218
Disease or Syndrome
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is characterized by progressive gastrointestinal dysmotility (manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain and/or distention, and diarrhea); cachexia; ptosis/ophthalmoplegia or ophthalmoparesis; leukoencephalopathy; and demyelinating peripheral neuropathy (manifesting as paresthesias (tingling, numbness, and pain) and symmetric and distal weakness more prominently affecting the lower extremities). The order in which manifestations appear is unpredictable. Onset is usually between the first and fifth decades; in about 60% of individuals, symptoms begin before age 20 years.
SHORT syndrome
MedGen UID:
164212
Concept ID:
C0878684
Disease or Syndrome
SHORT syndrome is a mnemonic for short stature, hyperextensibility, ocular depression (deeply set eyes), Rieger anomaly, and teething delay. It is now recognized that the features most consistently observed in SHORT syndrome are mild intrauterine growth restriction (IUGR); mild short stature; partial lipodystrophy (evident at birth in the face, and later in the chest and upper extremities, often sparing the buttocks and legs); and a characteristic facial gestalt. Other frequent features include: Axenfeld-Rieger anomaly or related ocular anterior chamber dysgenesis; delayed dentition and a variety of dental abnormalities; insulin resistance (typically in mid-childhood to adolescence) and/or diabetes mellitus in early adulthood; and sensorineural hearing loss. To date the diagnosis has been molecularly confirmed in individuals from 16 families; thus, the current understanding of the phenotypic spectrum and natural history are likely to evolve over time.
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 1
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).
Autosomal recessive keratitis-ichthyosis-deafness syndrome
MedGen UID:
224809
Concept ID:
C1275089
Disease or Syndrome
Keratitis-ichthyosis-deafness (KID) syndrome is characterized by eye problems, skin abnormalities, and hearing loss.People with KID syndrome usually have keratitis, which is inflammation of the front surface of the eye (the cornea). The keratitis may cause pain, increased sensitivity to light (photophobia), abnormal blood vessel growth over the cornea (neovascularization), and scarring. Over time, affected individuals experience a loss of sharp vision (reduced visual acuity); in severe cases the keratitis can lead to blindness.Most people with KID syndrome have thick, hard skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Affected individuals also have thick, reddened patches of skin (erythrokeratoderma) that are dry and scaly (ichthyosis). These dry patches can occur anywhere on the body, although they most commonly affect the neck, groin, and armpits. Breaks in the skin often occur and may lead to infections. In severe cases these infections can be life-threatening, especially in infancy. Approximately 12 percent of people with KID syndrome develop a type of skin cancer called squamous cell carcinoma, which may also affect mucous membranes such as the lining of the mouth.Partial hair loss is a common feature of KID syndrome, and often affects the eyebrows and eyelashes. Affected individuals may also have small, abnormally formed nails.Hearing loss in this condition is usually profound, but occasionally is less severe.
Deficiency of glycerate kinase
MedGen UID:
226941
Concept ID:
C1291386
Disease or Syndrome
D-glyceric aciduria is a rare autosomal recessive metabolic disorder with a highly variable phenotype. Some patients have an encephalopathic presentation, with severe mental retardation, seizures, microcephaly, and sometimes early death, whereas others have a mild phenotype with only mild speech delay or even normal development (summary by Sass et al., 2010).
WT limb blood syndrome
MedGen UID:
231231
Concept ID:
C1327917
Disease or Syndrome
Deafness, autosomal dominant 33
MedGen UID:
473419
Concept ID:
C1414002
Gene or Genome
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.
Alport syndrome, X-linked recessive
MedGen UID:
292688
Concept ID:
C1567742
Disease or Syndrome
Alport syndrome (AS) is characterized by renal, cochlear, and ocular involvement. In the absence of treatment, renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with X-linked (XL) AS, and in all males and females with autosomal recessive (AR) AS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In individuals with autosomal dominant (AD) AS, ESRD is frequently delayed until later adulthood, SNHL is also relatively late in onset and ocular involvement is rare. Thin basement membrane nephropathy (TBMN) is characterized by persistent microscopic hematuria often first observed in childhood; progressive renal disease is relatively unusual and extrarenal abnormalities are rare.
Alport syndrome, autosomal dominant
MedGen UID:
339210
Concept ID:
C1567743
Disease or Syndrome
Alport syndrome (AS) is characterized by renal, cochlear, and ocular involvement. In the absence of treatment, renal disease progresses from microscopic hematuria to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with X-linked (XL) AS, and in all males and females with autosomal recessive (AR) AS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In individuals with autosomal dominant (AD) AS, ESRD is frequently delayed until later adulthood, SNHL is also relatively late in onset and ocular involvement is rare. Thin basement membrane nephropathy (TBMN) is characterized by persistent microscopic hematuria often first observed in childhood; progressive renal disease is relatively unusual and extrarenal abnormalities are rare.
Usher syndrome, type 1
MedGen UID:
292820
Concept ID:
C1568247
Congenital Abnormality
Usher syndrome type I is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa. Unless fitted with a cochlear implant, individuals do not typically develop speech. Retinitis pigmentosa (RP), a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in progressively constricted visual fields and impaired visual acuity.
Usher syndrome, type 3A
MedGen UID:
339336
Concept ID:
C1568248
Disease or Syndrome
Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995). For a discussion of phenotypic heterogeneity of Usher syndrome, see USH1 (276900). Genetic Heterogeneity of Usher syndrome Type III Usher syndrome type IIIB (614504) is caused by mutation in the HARS gene (142810) on chromosome 5q31.3.
Duane-radial ray syndrome
MedGen UID:
301647
Concept ID:
C1623209
Disease or Syndrome
SALL4-related disorders include Duane-radial ray syndrome (DRRS, Okihiro syndrome), acro-renal-ocular syndrome (AROS), and SALL4-related Holt-Oram syndrome (HOS), three phenotypes previously thought to be distinct entities: DRRS is characterized by uni- or bilateral Duane anomaly and radial ray malformation that can include thenar hypoplasia and/or hypoplasia or aplasia of the thumbs, hypoplasia or aplasia of the radii, shortening and radial deviation of the forearms, triphalangeal thumbs, and duplication of the thumb (preaxial polydactyly). AROS is characterized by radial ray malformations, renal abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, vesico-ureteral reflux, bladder diverticula), ocular coloboma, and Duane anomaly. Rarely, pathogenic variants in SALL4 may cause clinically typical HOS (i.e., radial ray malformations and cardiac malformations without additional features).
Deafness, Y-linked 1
MedGen UID:
321613
Concept ID:
C1824927
Gene or Genome
Deafness, autosomal dominant 12
MedGen UID:
321902
Concept ID:
C1832187
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Peroxisome biogenesis disorders, Zellweger syndrome spectrum
MedGen UID:
330407
Concept ID:
C1832200
Disease or Syndrome
Peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD, ZSS) is a continuum comprising 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.
Athabaskan brainstem dysgenesis
MedGen UID:
330410
Concept ID:
C1832215
Disease or Syndrome
Van Maldergem syndrome 1
MedGen UID:
318616
Concept ID:
C1832390
Disease or Syndrome
Van Maldergem syndrome is an autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia (summary by Cappello et al., 2013). Genetic Heterogeneity of Van Maldergem Syndrome See also VMLDS2 (615546), caused by mutation in the FAT4 gene (612411) on chromosome 4q28.
Chitty Hall Baraitser syndrome
MedGen UID:
371330
Concept ID:
C1832438
Disease or Syndrome
This syndrome has characteristics of sensorineural deafness, short stature, femoral epiphyseal dysplasia, umbilical and inguinal hernias and developmental delay (growth retardation and mild intellectual deficit). It has been described in two brothers born to consanguineous parents. They also have dysmorphic features (triangular face, pointed chin) and bilateral obstruction of lacrimal ducts. This syndrome is transmitted as an autosomal recessive trait.
Deafness, autosomal dominant 10
MedGen UID:
321966
Concept ID:
C1832476
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Ayme-gripp syndrome
MedGen UID:
371416
Concept ID:
C1832812
Disease or Syndrome
Ayme-Gripp syndrome is a clinically homogeneous phenotype characterized by congenital cataracts, sensorineural hearing loss, intellectual disability, seizures, brachycephaly, a distinctive flat facial appearance, and reduced growth (Niceta et al., 2015).
Deafness, autosomal recessive 8
MedGen UID:
322046
Concept ID:
C1832827
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Deafness, autosomal recessive 9
MedGen UID:
331376
Concept ID:
C1832828
Disease or Syndrome
OTOF-related deafness (DFNB9 nonsyndromic hearing loss) is characterized by two phenotypes: prelingual nonsyndromic hearing loss and, less frequently, temperature-sensitive nonsyndromic auditory neuropathy (TS-NSAN). The nonsyndromic hearing loss is bilateral severe-to-profound congenital deafness. In the first one or two years of life, OTOF-related deafness can appear to be an auditory neuropathy based on electrophysiologic testing in which auditory brain stem responses (ABRs) are absent and otoacoustic emissions (OAEs) are present. However, with time OAEs disappear and electrophysiologic testing is more consistent with a cochlear defect. The distinction between auditory neuropathy and a cochlear defect is important as cochlear implants may be of marginal value in persons with auditory neuropathy but have been shown to be effective for individuals with OTOF-related deafness. TS-NSAN is characterized by normal-to-mild hearing loss in the absence of fever and significant hearing loss ranging from severe to profound in the presence of fever. When the fever resolves, hearing returns to normal.
Deafness, autosomal recessive 7
MedGen UID:
322084
Concept ID:
C1832978
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Deafness, autosomal recessive 5
MedGen UID:
331485
Concept ID:
C1833319
Disease or Syndrome
Hypertryptophanemia, familial
MedGen UID:
322223
Concept ID:
C1833562
Disease or Syndrome
Otodental dysplasia
MedGen UID:
318937
Concept ID:
C1833693
Disease or Syndrome
Otodental syndrome is an autosomal dominant condition characterized by grossly enlarged canine and molar teeth (globodontia), associated with sensorineural hearing loss. Ocular coloboma segregating with otodental syndrome has been reported (summary by Gregory-Evans et al., 2007).
Oculopharyngodistal myopathy
MedGen UID:
320250
Concept ID:
C1834014
Disease or Syndrome
Oculopharyngodistal myopathy (OPDM) is characterized by adult-onset of eye and facial muscle weakness, distal muscle weakness and atrophy, and pharyngeal involvement, resulting in dysphagia and dysarthria. There are variable manifestations of the disorder regarding muscle involvement and severity. Both autosomal recessive and autosomal dominant inheritance have been reported. OPDM is considered distinct from oculopharyngeal muscular dystrophy (OPMD; 164300), which is caused by mutation in the PABPN1 gene (602279) (summary by Durmus et al., 2011).
Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 1
MedGen UID:
371919
Concept ID:
C1834846
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. These phenotypes exemplify the diversity that can result from mutation of a given gene. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life up to about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, Parkinsonism, hypogonadism, and cataracts (in what has been called “chronic progressive external ophthalmoplegia plus,” or “CPEO+”).
Keratitis-ichthyosis-deafness syndrome, autosomal dominant
MedGen UID:
332032
Concept ID:
C1835678
Disease or Syndrome
Keratitis-ichthyosis-deafness (KID) syndrome is characterized by eye problems, skin abnormalities, and hearing loss.People with KID syndrome usually have keratitis, which is inflammation of the front surface of the eye (the cornea). The keratitis may cause pain, increased sensitivity to light (photophobia), abnormal blood vessel growth over the cornea (neovascularization), and scarring. Over time, affected individuals experience a loss of sharp vision (reduced visual acuity); in severe cases the keratitis can lead to blindness.Most people with KID syndrome have thick, hard skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Affected individuals also have thick, reddened patches of skin (erythrokeratoderma) that are dry and scaly (ichthyosis). These dry patches can occur anywhere on the body, although they most commonly affect the neck, groin, and armpits. Breaks in the skin often occur and may lead to infections. In severe cases these infections can be life-threatening, especially in infancy. Approximately 12 percent of people with KID syndrome develop a type of skin cancer called squamous cell carcinoma, which may also affect mucous membranes such as the lining of the mouth.Partial hair loss is a common feature of KID syndrome, and often affects the eyebrows and eyelashes. Affected individuals may also have small, abnormally formed nails.Hearing loss in this condition is usually profound, but occasionally is less severe.
Deafness, autosomal recessive 68
MedGen UID:
324374
Concept ID:
C1835854
Disease or Syndrome
Aminoacylase 1 deficiency
MedGen UID:
324393
Concept ID:
C1835922
Disease or Syndrome
Aminoacylase-1 deficiency (ACY1D) is a rare autosomal recessive inborn error of metabolism characterized by increased urinary excretion of specific N-actyl amino acids. Most patients show neurologic abnormalities such as intellectual disability, seizures, hypotonia, and motor delay (summary by Ferri et al., 2014).
Deafness, autosomal recessive 23
MedGen UID:
332110
Concept ID:
C1836027
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome
MedGen UID:
332113
Concept ID:
C1836033
Disease or Syndrome
CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome refers to a unique constellation of clinical manifestations including microcephaly, severe neurologic impairment, psychomotor retardation, failure to thrive, and facial dysmorphism, as well as palmoplantar keratoderma and late-onset ichthyosis. Brain magnetic resonance imaging (MRI) shows various degrees of cerebral dysgenesis including absence of corpus callosum and cortical dysplasia. The syndrome has been found to be uniformly fatal between the ages of 5 and 12 years (Fuchs-Telem et al., 2011).
Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions 2
MedGen UID:
322925
Concept ID:
C1836460
Disease or Syndrome
Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Both autosomal dominant and autosomal recessive inheritance can occur; autosomal recessive inheritance is usually more severe (Filosto et al., 2003; Luoma et al., 2004). PEO caused by mutations in the POLG gene are associated with more complicated phenotypes than those forms caused by mutations in the ANT1 or C10ORF2 genes (Lamantea et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640).
Kanzaki disease
MedGen UID:
324539
Concept ID:
C1836522
Disease or Syndrome
Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder with atypical features. It is clinically heterogeneous with 3 main phenotypes: type I is an infantile-onset neuroaxonal dystrophy (609241); type II, also known as Kanzaki disease, is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment; and type III is an intermediate disorder (see 609241) with mild to moderate neurologic manifestations (Desnick and Schindler, 2001).
Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease
MedGen UID:
373160
Concept ID:
C1836727
Disease or Syndrome
PCWH 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.
Auditory neuropathy, autosomal dominant, 1
MedGen UID:
322984
Concept ID:
C1836743
Disease or Syndrome
Auditory neuropathy is a type of hearing loss defined by the preservation of cochlear outer hair cell function and abnormal or absent auditory brainstem responses. Auditory neuropathy may accompany peripheral neuropathy in a variety of dominant syndromes such as Charcot-Marie-Tooth disease (Satya-Murti et al., 1979) and has been observed in Friedreich ataxia (Satya-Murti et al., 1980). Auditory neuropathy unassociated with peripheral neuropathy most commonly occurs as a sporadic or recessive trait; see, for example, 601071.
Nephropathy with pretibial epidermolysis bullosa and deafness
MedGen UID:
323004
Concept ID:
C1836823
Disease or Syndrome
Deafness, autosomal recessive 36, with or without vestibular involvement
MedGen UID:
324662
Concept ID:
C1837007
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Insulin-like growth factor I deficiency
MedGen UID:
373337
Concept ID:
C1837475
Disease or Syndrome
Deafness, autosomal dominant 28
MedGen UID:
324846
Concept ID:
C1837640
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Deafness, autosomal recessive 35
MedGen UID:
324897
Concept ID:
C1837857
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Brachydactyly-Mental Retardation syndrome
MedGen UID:
373895
Concept ID:
C1838126
Disease or Syndrome
2q37 microdeletion syndrome is characterized by mild-moderate developmental delay/intellectual disability, brachymetaphalangy of digits 3-5 (often digit 4 alone) (>50%), short stature, obesity, hypotonia, characteristic facial appearance, autism or autism spectrum disorder (30%), joint hypermobility/dislocation, and scoliosis. Other findings include seizures (20%-35%), congenital heart disease, CNS abnormalities (hydrocephalus, dilated ventricles), umbilical/inguinal hernia, tracheomalacia, situs abnormalities, gastrointestinal abnormalities, and renal malformations. Wilms tumor has been reported in two individuals.
CODAS syndrome
MedGen UID:
333031
Concept ID:
C1838180
Disease or Syndrome
CODAS is an acronym for cerebral, ocular, dental, auricular, and skeletal anomalies. CODAS syndrome is a rare disorder characterized by a distinctive constellation of features that includes developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts (summary by Strauss et al., 2015).
Waardenburg syndrome type 2B
MedGen UID:
373973
Concept ID:
C1838447
Disease or Syndrome
Waardenburg syndrome type II (WS2) is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (Hughes et al., 1994). WS type 2B (WS2B) maps to chromosome 1p. Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580).
Deafness, autosomal recessive 2
MedGen UID:
325485
Concept ID:
C1838701
Disease or Syndrome
Wolfram syndrome, mitochondrial form
MedGen UID:
325511
Concept ID:
C1838782
Disease or Syndrome
Mitochondrial complex I deficiency
MedGen UID:
374101
Concept ID:
C1838979
Disease or Syndrome
Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). Genetic Heterogeneity of Complex I Deficiency Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). Complex I deficiency with autosomal recessive inheritance results from mutation in nuclear-encoded subunit genes, including NDUFV1 (161015), NDUFV2 (600532), NDUFS1 (157655), NDUFS2 (602985), NDUFS3 (603846), NDUFS4 (602694), NDUFS6 (603848), NDUFS7 (601825), NDUFS8 (602141), NDUFA2 (602137), NDUFA11 (612638), NDUFAF3 (612911), NDUFA10 (603835), NDUFB3 (603839), NDUFB9 (601445), and the complex I assembly genes B17.2L (609653), HRPAP20 (611776), C20ORF7 (612360), NUBPL (613621), NDUFAF1 (606934), and TMEM126B (615533). The disorder can also be caused by mutation in other nuclear-encoded genes, including FOXRED1 (613622), ACAD9 (611103; see 611126), and MTFMT (611766; see 256000). X-linked inheritance is observed with mutations in the NDUFA1 (300078) and NDUFB11 (300403) genes. Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (516000), MTND2 (516001), MTND3 (516002), MTND4 (516003), MTND5 (516005), MTND6 (516006). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; 535000) or Leigh syndrome (256000). Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (590085).
Charcot-Marie-Tooth disease, X-linked recessive, type 5
MedGen UID:
374254
Concept ID:
C1839566
Disease or Syndrome
Charcot-Marie-Tooth (CMT) hereditary neuropathy refers to a group of disorders characterized by a chronic motor and sensory polyneuropathy. The affected individual typically has distal muscle weakness and atrophy often associated with mild to moderate sensory loss, depressed tendon reflexes, and high-arched feet.
Barakat syndrome
MedGen UID:
374443
Concept ID:
C1840333
Disease or Syndrome
Branchiootic syndrome 3
MedGen UID:
333995
Concept ID:
C1842124
Disease or Syndrome
Branchiootorenal spectrum disorders comprise branchiootorenal (BOR) syndrome and branchiootic syndrome (BOS). BOR is characterized by malformations of the outer, middle, and inner ear associated with conductive, sensorineural, or mixed hearing impairment, branchial fistulae and cysts, and renal malformations ranging from mild renal hypoplasia to bilateral renal agenesis. Some individuals progress to end-stage renal disease (ESRD) later in life. BOS has the same features as BOR syndrome but without renal involvement. Extreme variability can be observed in the presence, severity, and type of branchial arch, otologic, audiologic, and renal abnormality from right side to left side in an affected individual and also among individuals in the same family. BOR syndrome and BOS can be seen in the same family.
Deafness, autosomal dominant 49
MedGen UID:
331222
Concept ID:
C1842136
Disease or Syndrome
Lipodystrophy, generalized, with mental retardation, deafness, short stature, and slender bones
MedGen UID:
334166
Concept ID:
C1842465
Disease or Syndrome
Neuropathy, hereditary sensory and autonomic, type I, with cough and gastroesophageal reflux
MedGen UID:
330880
Concept ID:
C1842586
Disease or Syndrome
The hereditary sensory and autonomic neuropathies (HSAN), which are also referred to as hereditary sensory neuropathies (HSN) in the absence of significant autonomic features, are a genetically and clinically heterogeneous group of disorders associated with sensory dysfunction. For a discussion of genetic heterogeneity of HSAN, see HSAN1A (162400).
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%).
Deafness, autosomal dominant 48
MedGen UID:
375052
Concept ID:
C1842939
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Charcot-Marie-Tooth disease type 2J
MedGen UID:
375107
Concept ID:
C1843153
Disease or Syndrome
Charcot-Marie-Tooth hereditary neuropathy type 2 (CMT2) is an axonal (non-demyelinating) peripheral neuropathy characterized by distal muscle weakness and atrophy, mild sensory loss, and normal or near-normal nerve conduction velocities. CMT2 is clinically similar to CMT1, although typically less severe. Peripheral nerves are not enlarged or hypertrophic. The subtypes of CMT2 are similar clinically and distinguished only by molecular genetic findings.
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
MedGen UID:
375302
Concept ID:
C1843851
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. These phenotypes exemplify the diversity that can result from mutation of a given gene. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life up to about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, Parkinsonism, hypogonadism, and cataracts (in what has been called “chronic progressive external ophthalmoplegia plus,” or “CPEO+”).
Deafness, autosomal dominant 44
MedGen UID:
334525
Concept ID:
C1843895
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Coenzyme Q10 deficiency, primary 1
MedGen UID:
334528
Concept ID:
C1843920
Disease or Syndrome
Primary CoQ10 deficiency is a rare, clinically heterogeneous autosomal recessive disorder caused by mutation in any of the genes encoding proteins directly involved in the synthesis of coenzyme Q (review by Quinzii and Hirano, 2011). Coenzyme Q10 (CoQ10), or ubiquinone, is a mobile lipophilic electron carrier critical for electron transfer by the mitochondrial inner membrane respiratory chain (Duncan et al., 2009). The disorder has been associated with 5 major phenotypes, but the molecular basis has not been determined in most patients with the disorder and there are no clear genotype/phenotype correlations. The phenotypes include an encephalomyopathic form with seizures and ataxia (Ogasahara et al., 1989); a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure (Rotig et al., 2000); a predominantly cerebellar form with ataxia and cerebellar atrophy (Lamperti et al., 2003); Leigh syndrome with growth retardation (van Maldergem et al., 2002); and an isolated myopathic form (Lalani et al., 2005). The correct diagnosis is important because some patients may show a favorable response to CoQ10 treatment. Genetic Heterogeneity of Primary Coenzyme Q10 Deficiency See also COQ10D2 (614651), caused by mutation in the PDSS1 gene (607429) on chromosome 10p12; COQ10D3 (614652), caused by mutation in the PDSS2 gene (610564) on chromosome 6q21; COQ10D4 (612016), caused by mutation in the COQ8 gene (ADCK3; 606980) on chromosome 1q42; COQ10D5 (614654), caused by mutation in the COQ9 gene (612837) on chromosome 16q21; COQ10D6 (614650), caused by mutation in the COQ6 gene (614647) on chromosome 14q24; COQ10D7 (616276), caused by mutation in the COQ4 gene (612898) on chromosome 9q34; and COQ10D8 (616733), caused by mutation in the COQ7 gene (601683) on chromosome 16p13. Secondary CoQ10 deficiency has been reported in association with glutaric aciduria type IIC (MADD; 231680), caused by mutation in the ETFDH gene (231675) on chromosome 4q, and with ataxia-oculomotor apraxia syndrome-1 (AOA1; 208920), caused by mutation in the APTX gene (606350) on chromosome 9p13.
Deafness, X-linked 1
MedGen UID:
336749
Concept ID:
C1844677
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Spinocerebellar ataxia X-linked type 3
MedGen UID:
337124
Concept ID:
C1844936
Disease or Syndrome
A progressive disorder of the central nervous system characterized by ataxia, deafness, hypotonia, developmental delay, esotropia, and optic atrophy.
ATR-X syndrome
MedGen UID:
337145
Concept ID:
C1845055
Disease or Syndrome
Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome is characterized by distinctive craniofacial features, genital anomalies, severe developmental delays, hypotonia, intellectual disability, and mild-to-moderate anemia secondary to alpha-thalassemia. Craniofacial abnormalities include small head circumference, telecanthus or widely spaced eyes, short nose, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip with coarsening of the facial features over time. Although all affected individuals have a normal 46,XY karyotype, genital anomalies range from hypospadias and undescended testicles to severe hypospadias and ambiguous genitalia, to normal-appearing female external genitalia. Global developmental delays are evident in infancy and some affected individuals never walk independently or develop significant speech.
Chromosome Xq28 deletion syndrome
MedGen UID:
336933
Concept ID:
C1845408
Disease or Syndrome
Deafness, dystonia, and cerebral hypomyelination is an X-linked recessive mental retardation syndrome characterized by almost no psychomotor development, dysmorphic facial features, sensorineural deafness, dystonia, pyramidal signs, and hypomyelination on brain imaging (summary by Cacciagli et al., 2013).
Corpus callosum, agenesis of, with mental retardation, ocular coloboma, and micrognathia
MedGen UID:
335185
Concept ID:
C1845446
Disease or Syndrome
2-methyl-3-hydroxybutyric aciduria
MedGen UID:
336957
Concept ID:
C1845517
Disease or Syndrome
HSD10 deficiency is an X-linked dominant neurodegenerative disorder characterized by onset in late infancy or childhood. The severity is highly variable, but some patients have slow loss of developmental skills, cardiomyopathy, retinal degeneration, and seizures; the features resemble a mitochondrial disorder. Unlike other organic acidurias, most patients do not develop severe metabolic crises in the neonatal period (summary by Rauschenberger et al., 2010).
Mental retardation 46, X-linked
MedGen UID:
337255
Concept ID:
C1845526
Disease or Syndrome
FG syndrome 4
MedGen UID:
336965
Concept ID:
C1845546
Disease or Syndrome
FG syndrome-4 is an X-linked recessive mental retardation syndrome characterized by congenital hypotonia, constipation, behavioral disturbances, and dysmorphic features (summary by Piluso et al., 2003). The name 'FG' derives from the first description of the disorder (FGS1; 305450) by Opitz and Kaveggia (1974), who named it 'FG syndrome' according to the Opitz system of using initials of patients' surnames. For a phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (305450). FGS4 is typically associated with missense or hypomorphic mutations in the CASK gene. See also the more severe disorder MICPCH (300749), an allelic disorder caused by complete loss-of-function mutations in the CASK gene (Tarpey et al., 2009).
Oculofaciocardiodental syndrome
MedGen UID:
337547
Concept ID:
C1846265
Disease or Syndrome
Lenz microphthalmia syndrome (LMS) is characterized by unilateral or bilateral microphthalmia and/or clinical anophthalmia with malformations of the ears, teeth, fingers, skeleton, and/or genitourinary system. Microphthalmia is often accompanied by microcornea and glaucoma. Coloboma is present in approximately 60% of microphthalmic eyes with severity ranging from isolated iris coloboma to coloboma of the ciliary body, choroid, and optic disk. Ears may be low set, anteverted, posteriorly rotated, simple, cup shaped, or abnormally modeled. Hearing loss has been observed. Dental findings include irregularly shaped, missing, or widely spaced teeth. Duplicated thumbs, syndactyly, clinodactyly, camptodactyly, and microcephaly are common, as are narrow/sloping shoulders, underdeveloped clavicles, kyphoscoliosis, exaggerated lumbar lordosis, long cylindric thorax, and webbed neck. Genitourinary anomalies include hypospadias, cryptorchidism, renal hypoplasia/aplasia, and hydroureter. Approximately 60% of affected males have mild-to-severe intellectual disability or developmental delay.
Juvenile-onset dystonia
MedGen UID:
339494
Concept ID:
C1846331
Disease or Syndrome
Deafness, autosomal recessive 31
MedGen UID:
339621
Concept ID:
C1846839
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Deafness, autosomal recessive 22
MedGen UID:
339636
Concept ID:
C1846896
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Deafness, autosomal dominant 21
MedGen UID:
339643
Concept ID:
C1846922
Disease or Syndrome
Usher syndrome, type 1G
MedGen UID:
339683
Concept ID:
C1847089
Disease or Syndrome
Usher syndrome type I is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa. Unless fitted with a cochlear implant, individuals do not typically develop speech. Retinitis pigmentosa (RP), a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in progressively constricted visual fields and impaired visual acuity.
Deafness, autosomal dominant 36
MedGen UID:
376173
Concept ID:
C1847626
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Deafness, X-linked 4
MedGen UID:
376307
Concept ID:
C1848204
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Weissenbacher-Zweymuller syndrome
MedGen UID:
341234
Concept ID:
C1848488
Congenital Abnormality
Weissenbacher-Zweymüller syndrome is a condition that affects bone growth. It is characterized by skeletal abnormalities, hearing loss, and distinctive facial features. The features of this condition significantly overlap those of two similar conditions, otospondylomegaepiphyseal dysplasia (OSMED) and Stickler syndrome type III. All of these conditions are caused by mutations in the same gene, and in some cases, it can be difficult to tell them apart. Some researchers believe they represent a single disorder with a range of signs and symptoms.Infants born with Weissenbacher-Zweymüller syndrome are smaller than average because the bones in their arms and legs are unusually short. The thigh and upper arm bones are wider than usual at the ends (described as dumbbell-shaped), and the bones of the spine (vertebrae) may also be abnormally shaped. High-frequency hearing loss occurs in some cases. Distinctive facial features include wide-set protruding eyes, a small and upturned nose with a flat bridge, and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth (a cleft palate).Most people with Weissenbacher-Zweymüller syndrome experience significant "catch-up" growth in the bones of the arms and legs during childhood. As a result, adults with this condition are not unusually short. However, affected adults still have other signs and symptoms of Weissenbacher-Zweymüller syndrome, including distinctive facial features and hearing loss.
Waardenburg syndrome type 4A
MedGen UID:
341244
Concept ID:
C1848519
Disease or Syndrome
Waardenburg syndrome type 4 (WS4), also known as Waardenburg-Shah syndrome, is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 4A is caused by mutation in the EDNRB gene (131244). Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III (WS3; 148820) has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type 4 has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010). Genetic Heterogeneity of Waardenburg Syndrome Type 4 Waardenburg syndrome type 4 is genetically heterogeneous. WS4B (613265) is caused by mutation in the EDN3 gene (131242) on chromosome 20q13, and WS4C (613266) is caused by mutation in the SOX10 gene (602229) on chromosome 22q13.
Thyrocerebral-retinal syndrome
MedGen UID:
341311
Concept ID:
C1848813
Disease or Syndrome
Ataxia, spastic, childhood-onset, autosomal recessive, with optic atrophy and mental retardation
MedGen UID:
376528
Concept ID:
C1849156
Disease or Syndrome
This progressive neurodegenerative disorder is characterized by early childhood onset of spastic ataxia with mental retardation, cerebellar signs, and variable optic atrophy (Hogan and Bauman, 1977).
Retinitis pigmentosa inversa with deafness
MedGen UID:
341447
Concept ID:
C1849405
Disease or Syndrome
Nephropathy deafness hyperparathyroidism
MedGen UID:
340569
Concept ID:
C1850553
Disease or Syndrome
Nasodigitoacoustic syndrome
MedGen UID:
338088
Concept ID:
C1850627
Disease or Syndrome
Keipert syndrome is characterized by brachydactyly, broad thumbs and halluces, hypertelorism and other minor facial dysmorphic features, and sensorineural deafness. Phenotypically related syndromes include Teunissen-Cremers syndrome (184460), Muenke syndrome (602849) and Keutel syndrome (245150) (Nik-Zainal et al., 2008).
Friedreich ataxia, so-called, with optic atrophy and sensorineural deafness
MedGen UID:
376920
Concept ID:
C1850982
Disease or Syndrome
Deafness, autosomal dominant 1
MedGen UID:
343767
Concept ID:
C1852282
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Deafness, mid-tone neural
MedGen UID:
338897
Concept ID:
C1852283
Disease or Syndrome
Craniofacial deafness hand syndrome
MedGen UID:
377694
Concept ID:
C1852510
Disease or Syndrome
Craniofacial-deafness-hand syndrome is characterized by distinctive facial features, profound hearing loss, and hand abnormalities.The distinctive facial features of people with craniofacial-deafness-hand syndrome result from a variety of developmental abnormalities involving the skull (cranium) and face. Affected individuals often have underdeveloped or absent nasal bones resulting in a small nose, thin nostrils, and a flattened mid-face with a flat nasal bridge. Individuals with this condition typically also have widely spaced eyes (ocular hypertelorism), narrowed openings of the eyes (narrowed palpebral fissures), a small upper jaw (hypoplastic maxilla), and a small mouth with pursed lips.People with this condition also have profound hearing loss that is caused by abnormalities in the inner ear (sensorineural deafness). Hearing loss in these individuals is present from birth.In affected individuals, a common abnormality of the muscles in the hand is a malformation in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). People with craniofacial-deafness-hand syndrome may also have permanently bent third, fourth, and fifth fingers (camptodactyly), which can limit finger movement and lead to joint deformities called contractures. Contractures in the wrist can further impair hand movements.
Corneal hypesthesia with retinal abnormalities, sensorineural deafness, unusual facies, persistent ductus arteriosus, and mental retardation
MedGen UID:
342261
Concept ID:
C1852543
Disease or Syndrome
Renal coloboma syndrome
MedGen UID:
339002
Concept ID:
C1852759
Disease or Syndrome
Renal coloboma (papillorenal syndrome) is an autosomal dominant condition characterized by renal hypodysplasia and abnormalities of the optic nerve. Abnormal renal structure or function is noted in 92% of affected individuals; ophthalmologic abnormalities are noted in 77% of affected individuals who have pathogenic variants in PAX2. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency/renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with a PAX2 pathogenic variant. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include hearing loss, which is noted in 7% of individuals with identified pathogenic variants in PAX2.
Stickler syndrome, type 4
MedGen UID:
342319
Concept ID:
C1852831
Disease or Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Neutral lipid storage disease with myopathy
MedGen UID:
339913
Concept ID:
C1853136
Disease or Syndrome
Neutral lipid storage disease with myopathy is an autosomal recessive muscle disorder characterized by adult onset of slowly progressive proximal muscle weakness affecting the upper and lower limbs and associated with increased serum creatine kinase; distal muscle weakness may also occur. About half of patients develop cardiomyopathy later in the disease course. Other variable features include diabetes mellitus, hepatic steatosis, hypertriglyceridemia, and possibly sensorineural hearing loss. Leukocytes and muscle cells show cytoplasmic accumulation of triglycerides (summary by Reilich et al., 2011). Neutral lipid storage disease with myopathy belongs to a group of disorders termed neutral lipid storage disorders (NLSDs). These disorders are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Chanarin-Dorfman syndrome (CDS; 275630) is defined as NLSD with ichthyosis (NLSDI). Patients with NLSDM present with myopathy but without ichthyosis (summary by Fischer et al., 2007).
Deafness, autosomal recessive 67
MedGen UID:
343997
Concept ID:
C1853223
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Congenital disorder of glycosylation type 2B
MedGen UID:
342954
Concept ID:
C1853736
Disease or Syndrome
Spondyloocular syndrome, autosomal recessive
MedGen UID:
343011
Concept ID:
C1853925
Disease or Syndrome
Deafness, autosomal recessive 27
MedGen UID:
381303
Concept ID:
C1853941
Disease or Syndrome
Cutis Verticis Gyrata, Retinitis Pigmentosa, and Sensorineural Deafness
MedGen UID:
340123
Concept ID:
C1854061
Disease or Syndrome
Deafness, autosomal dominant 25
MedGen UID:
344221
Concept ID:
C1854158
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Radioulnar synostosis with amegakaryocytic thrombocytopenia
MedGen UID:
340183
Concept ID:
C1854273
Disease or Syndrome
Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm (summary by Niihori et al., 2015). Genetic Heterogeneity of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia Radioulnar synostosis with amegakaryocytic thrombocytopenia-2 (RUSAT2; 616738) is caused by heterozygous mutation in the MECOM gene (165215) on chromosome 3q26.
Dilated cardiomyopathy 1J
MedGen UID:
343105
Concept ID:
C1854368
Disease or Syndrome
Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal nocturnal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion). Arrhythmias and/or conduction system disease. Thromboembolic disease (from left ventricular mural thrombus) including stroke.
Deafness, autosomal dominant 23
MedGen UID:
343162
Concept ID:
C1854594
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Baraitser-Winter syndrome 1
MedGen UID:
340943
Concept ID:
C1855722
Disease or Syndrome
BRWS is a rare developmental phenotype characterized by the combination of hypertelorism, broad nose with large tip and prominent root, congenital nonmyopathic ptosis, ridged metopic suture, arched eyebrows, iris or retinal coloboma, sensorineural deafness, shoulder girdle muscle bulk and progressive joint stiffness, and pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Intellectual disability and epilepsy are variable in severity and largely correlate with central nervous system anomalies (summary by Verloes et al., 2015). Di Donato et al. (2014) and Verloes et al. (2015) suggested that BRWS, Fryns-Aftimos syndrome, and cerebrofrontofacial syndrome represent the same clinical entity. 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.
Absent corpus callosum cataract immunodeficiency
MedGen UID:
340962
Concept ID:
C1855772
Disease or Syndrome
Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum, cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy (summary by Finocchi et al., 2012).
Hyperphosphatasia with mental retardation syndrome 1
MedGen UID:
383800
Concept ID:
C1855923
Disease or Syndrome
Hyperphosphatasia with mental retardation syndrome-1 is an autosomal recessive disorder characterized by mental retardation, various neurologic abnormalities such as seizures and hypotonia, and hyperphosphatasia. Other features include facial dysmorphism and variable degrees of brachytelephalangy (summary by Krawitz et al., 2010). The disorder is caused by a defect in glycosylphosphatidylinositol biosynthesis; see GPIBD1 (610293). Genetic Heterogeneity of Hyperphosphatasia with Mental Retardation Syndrome See also HPMRS2 (614749), caused by mutation in the PIGO gene (614730) on chromosome 9p13; HPMRS3 (614207), caused by mutation in the PGAP2 gene (615187) on chromosome 11p15; HPMRS4 (615716), caused by mutation in the PGAP3 gene (611801) on chromosome 17q12; HPMRS5 (616025), caused by mutation in the PIGW gene (610275) on chromosome 17q12; and HPMRS6 (616809), caused by mutation in the PIGY gene (610662) on chromosome 4q22.
Deafness enamel hypoplasia nail defects
MedGen UID:
343498
Concept ID:
C1856186
Disease or Syndrome
Heimler syndrome-1 (HMLR1), which represents the mildest end of the peroxisomal biogenesis disorder spectrum (see PBD1A, 214100), is a rare autosomal recessive disorder characterized by sensorineural hearing loss, enamel hyoplasia of the secondary dentition, and nail abnormalities (Ratbi et al., 2015). Genetic Heterogeneity of Heimler Syndrome Another form of Heimler syndrome (HMLR2; 616617) is caused by mutation in the PEX6 gene (601498) on chromosome 6p21.
Ermine phenotype
MedGen UID:
346466
Concept ID:
C1856899
Disease or Syndrome
Ectodermal dysplasia and neurosensory deafness
MedGen UID:
346503
Concept ID:
C1857068
Disease or Syndrome
Disorganization, mouse, homolog of
MedGen UID:
387773
Concept ID:
C1857230
Disease or Syndrome
Donnai Barrow syndrome
MedGen UID:
347406
Concept ID:
C1857277
Disease or Syndrome
Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (ocular hypertelorism, enlarged fontanelle), ocular findings (high myopia, retinal detachment, progressive vision loss, and iris coloboma), sensorineural hearing loss, agenesis of the corpus callosum, intellectual disability, and congenital diaphragmatic hernia (CDH) and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed.
Pituitary hormone deficiency, combined 3
MedGen UID:
341749
Concept ID:
C1857330
Disease or Syndrome
Combined pituitary hormone deficiency is a condition that causes a shortage (deficiency) of several hormones produced by the pituitary gland, which is located at the base of the brain. A lack of these hormones may affect the development of many parts of the body. The first signs of this condition include a failure to grow at the expected rate and short stature that usually becomes apparent in early childhood.People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and fatigue. Other features of combined pituitary hormone deficiency include delayed or absent puberty and lack the ability to have biological children (infertility). The condition can also be associated with a deficiency of the hormone cortisol. Cortisol deficiency can impair the body's immune system, causing individuals to be more susceptible to infection.Rarely, people with combined pituitary hormone deficiency have intellectual disability; a short, stiff neck; or underdeveloped optic nerves, which carry visual information from the eyes to the brain.
Deafness, neural, with atypical atopic dermatitis
MedGen UID:
346567
Concept ID:
C1857334
Disease or Syndrome
Deafness, neural, congenital moderate
MedGen UID:
347425
Concept ID:
C1857337
Disease or Syndrome
Groll Hirschowitz syndrome
MedGen UID:
347426
Concept ID:
C1857338
Disease or Syndrome
Split-hand/foot malformation 1 with sensorineural hearing loss
MedGen UID:
347431
Concept ID:
C1857344
Disease or Syndrome
Digitorenocerebral syndrome
MedGen UID:
387800
Concept ID:
C1857345
Disease or Syndrome
TBC1D24-related disorders comprise a continuum that includes the following recognized phenotypes: DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures): profound sensorineural hearing loss, onychodystrophy, osteodystrophy, intellectual disability/developmental delay, and seizures. Familial infantile myoclonic epilepsy (FIME): early-onset myoclonic seizures, focal epilepsy, dysarthria, and mild-to-moderate intellectual disability. Progressive myoclonus epilepsy (PME): action myoclonus, tonic-clonic seizures, progressive neurologic decline, and ataxia. Early-infantile epileptic encephalopathy 16 (EIEE16): epileptiform EEG abnormalities which themselves are believed to contribute to progressive disturbance in cerebral function. Autosomal recessive nonsyndromic hearing loss, DFNB86: profound prelingual deafness. Autosomal dominant nonsyndromic hearing loss, DFNA65: slowly progressive deafness with onset in the third decade, initially affecting the high frequencies.
Craniosynostosis-mental retardation syndrome of Lin and Gettig
MedGen UID:
341781
Concept ID:
C1857473
Disease or Syndrome
Deafness, autosomal recessive 59
MedGen UID:
387899
Concept ID:
C1857744
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Spastic paraplegia 29
MedGen UID:
346682
Concept ID:
C1857855
Disease or Syndrome
Wolfram syndrome 2
MedGen UID:
347604
Concept ID:
C1858028
Disease or Syndrome
Wolfram syndrome-2 is an autosomal recessive neurodegenerative disorder characterized by diabetes mellitus, high frequency sensorineural hearing loss, optic atrophy or neuropathy, and defective platelet aggregation resulting in peptic ulcer bleeding (summary by Mozzillo et al., 2014). For a discussion of genetic heterogeneity of Wolfram syndrome, see WFS1 (222300).
Stickler syndrome, type 2
MedGen UID:
347615
Concept ID:
C1858084
Disease or Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Primary autosomal recessive microcephaly 3
MedGen UID:
347619
Concept ID:
C1858108
Disease or Syndrome
Primary autosomal recessive microcephalies (MCPH) and Seckel syndrome (SCKS) spectrum disorders are characterized by microcephaly and the absence of visceral malformations. Although MCHP and SCKS were previously distinguished by height (maximum height in SCKS was equivalent to the minimum height in MCPH), stature is no longer a discriminating feature, leading to the conclusion that these phenotypes constitute a spectrum rather than distinct entities. Microcephaly is characterized by: Onset during the second trimester of gestation; Occipito-frontal head circumference (OFC) at birth equal to or less than -2 SD below the mean for sex, age, and ethnicity; Slower than average increase in OFC after birth. Variable findings in the MCPH-SCKS spectrum disorders include: Brain structure (which is normal in the majority); Degree of cognitive impairment (usually mild to moderate without significant motor delay in the majority of persons with MCPH and more severe in those with SCKS and MCPH with brain malformations); Degree of short stature; Craniosynostosis (which may be secondary to poor brain growth).
Charcot-Marie-Tooth disease, type 4B2
MedGen UID:
346869
Concept ID:
C1858278
Disease or Syndrome
Charcot-Marie-Tooth neuropathy type 4 (CMT4) is a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Affected individuals have the typical CMT phenotype of distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity.
Blepharophimosis with facial and genital anomalies and mental retardation
MedGen UID:
347661
Concept ID:
C1858538
Disease or Syndrome
Cerebellar ataxia, deafness, and narcolepsy, autosomal dominant
MedGen UID:
347726
Concept ID:
C1858804
Disease or Syndrome
ADCADN is an autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy/cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression (summary by Winkelmann et al., 2012).
Deafness, autosomal recessive 20
MedGen UID:
347005
Concept ID:
C1858840
Disease or Syndrome
Rhizomelic chondrodysplasia punctata type 1
MedGen UID:
347072
Concept ID:
C1859133
Disease or Syndrome
Rhizomelic chondrodysplasia punctata type 1 (RCDP1) classic type, a peroxisome biogenesis disorder (PBD), is characterized by proximal shortening of the humerus and to a lesser degree the femur (rhizomelia), punctate calcifications in cartilage with epiphyseal and metaphyseal abnormalities (chondrodysplasia punctata, or CDP), coronal clefts of the vertebral bodies, and cataracts that are usually present at birth or appear in the first few months of life. Birth weight, length, and head circumference are often at the lower range of normal; postnatal growth deficiency is profound. Intellectual disability is severe, and the majority of children develop seizures. Most affected children do not survive the first decade of life; a proportion die in the neonatal period. A milder phenotype in which all affected individuals have congenital cataracts and chondrodysplasia is now recognized; some do not have rhizomelia, and some have less severe intellectual disability and growth deficiency.
Neuropathy, hereditary motor and sensory, with deafness, mental retardation, and absent sensory large myelinated fibers
MedGen UID:
347824
Concept ID:
C1859206
Disease or Syndrome
Klippel-Feil syndrome 2, autosomal recessive
MedGen UID:
395201
Concept ID:
C1859209
Disease or Syndrome
Klippel-Feil syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in a fused appearance. The clinical triad consists of short neck, low posterior hairline, and limited neck movement, although less than 50% of patients demonstrate all 3 clinical features (Tracy et al., 2004). Clarke et al. (1998) proposed a classification system for KFS in which an autosomal recessive form is characterized by the most rostral fusion at C1 and the presence of severe associated anomalies, including short neck, cardiac defects, and craniofacial anomalies. For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Cerebellar ataxia and neurosensory deafness
MedGen UID:
395224
Concept ID:
C1859304
Disease or Syndrome
Feigenbaum Bergeron Richardson syndrome
MedGen UID:
349198
Concept ID:
C1859596
Disease or Syndrome
Ataxia, deafness and cardiomyopathy
MedGen UID:
395312
Concept ID:
C1859645
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.
Kaplan Plauchu Fitch syndrome
MedGen UID:
349738
Concept ID:
C1860145
Disease or Syndrome
Stickler syndrome, type 3
MedGen UID:
349293
Concept ID:
C1861481
Congenital Abnormality
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Charcot-Marie-Tooth disease and deafness
MedGen UID:
348419
Concept ID:
C1861669
Disease or Syndrome
Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a demyelinating peripheral neuropathy characterized by distal muscle weakness and atrophy, sensory loss, and slow nerve conduction velocity. It is usually slowly progressive and often associated with pes cavus foot deformity and bilateral foot drop. Affected individuals usually become symptomatic between age five and 25 years. Fewer than 5% of individuals become wheelchair dependent. Life span is not shortened.
Spinocerebellar ataxia 31
MedGen UID:
348439
Concept ID:
C1861736
Disease or Syndrome
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosome locus) in which pathogenic variants occur.
Axenfeld-Rieger anomaly with partially absent eye muscles, distinctive face, hydrocephaly, and skeletal abnormalities
MedGen UID:
349489
Concept ID:
C1862373
Disease or Syndrome
Arthrogryposis-like hand anomaly and sensorineural deafness
MedGen UID:
350677
Concept ID:
C1862471
Disease or Syndrome
Distal arthrogryposis type 6 (DA6) is distinguished by the additional feature of sensorineural deafness (summary by Bamshad et al., 2009). For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Albinism, ocular, with sensorineural deafness
MedGen UID:
400230
Concept ID:
C1863198
Disease or Syndrome
Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss.
Deafness, autosomal recessive 16
MedGen UID:
350211
Concept ID:
C1863561
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Neuroendocrine carcinoma of salivary glands, sensorineural hearing loss, and enamel hypoplasia
MedGen UID:
355029
Concept ID:
C1863649
Neoplastic Process
Deafness, autosomal recessive 21
MedGen UID:
355030
Concept ID:
C1863655
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Enlarged vestibular aqueduct syndrome
MedGen UID:
355050
Concept ID:
C1863752
Finding
Pendred syndrome (PDS) and DFNB4 comprise a phenotypic spectrum of hearing loss with or without other findings. Pendred syndrome is characterized by: severe-to-profound bilateral sensorineural hearing impairment that is usually congenital (or prelingual) and non-progressive; vestibular dysfunction; temporal bone abnormalities; and development of euthyroid goiter in late childhood to early adulthood. Variability of findings is considerable, even within the same family. DFNB4 is characterized by nonsyndromic sensorineural hearing impairment, vestibular dysfunction, and enlarged vestibular aqueduct (EVA). Thyroid defects are not seen in DFNB4.
Craniosynostosis, anal anomalies, and porokeratosis
MedGen UID:
351066
Concept ID:
C1864186
Disease or Syndrome
Deafness, autosomal recessive 17
MedGen UID:
355180
Concept ID:
C1864276
Disease or Syndrome
Muenke syndrome
MedGen UID:
355217
Concept ID:
C1864436
Congenital Abnormality
Muenke syndrome is defined by the presence of the specific FGFR3 pathogenic variant – c.749C>G – that results in the protein change p.Pro250Arg. Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pan synostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (reduced anteroposterior dimension of the skull), although turribrachycephaly (a "tower-shaped" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: temporal bossing; widely spaced eyes, ptosis or proptosis (usually mild); midface retrusion (usually mild); and highly arched palate or cleft lip and palate. Strabismus is common. Other findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); epilepsy; intracranial anomalies; intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family. Of note, some individuals who have the p.Pro250Arg pathogenic variant may have no signs of Muenke syndrome on physical or radiographic examination.
Histiocytosis-lymphadenopathy plus syndrome
MedGen UID:
400532
Concept ID:
C1864445
Disease or Syndrome
The histiocytosis-lymphadenopathy plus syndrome comprises features of 4 histiocytic disorders previously thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC described an autosomal recessive disease involving joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes (summary by Morgan et al., 2010). SHML, or familial Rosai-Dorfman disease, was described as a rare cause of lymph node enlargement in children, consisting of chronic massive enlargement of cervical lymph nodes frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Extranodal sites were involved in approximately 25% of patients, including salivary glands, orbit, eyelid, spleen, and testes. The involvement of retropharyngeal lymphoid tissue sometimes caused snoring and sleep apnea (summary by Kismet et al., 2005). H syndrome was characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss was also found in about half of patients, and many had short stature. PHID was characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome, with hepatosplenomegaly occurring in about half of patients (Cliffe et al., 2009). Bolze et al. (2012) noted that mutations in the SLC29A3 gene (612373) had been implicated in H syndrome, PHID, FHC, and SHML, and that some patients presented a combination of features from 2 or more of these syndromes, leading to the suggestion that these phenotypes should be grouped together as 'SLC29A3 disorder.' Bolze et al. (2012) suggested that the histologic features of the lesions seemed to be the most uniform phenotype in these patients. In addition, the immunophenotype of infiltrating cells in H syndrome patients was shown to be the same as that seen in patients with the familial form of Rosai-Dorfman disease, further supporting the relationship between these disorders (Avitan-Hersh et al., 2011; Colmenero et al., 2012).
Deafness, autosomal recessive 53
MedGen UID:
400602
Concept ID:
C1864746
Disease or Syndrome
Deafness, autosomal recessive 42
MedGen UID:
351225
Concept ID:
C1864818
Disease or Syndrome
Camptodactyly, tall stature, and hearing loss syndrome
MedGen UID:
355844
Concept ID:
C1864852
Disease or Syndrome
Ectodermal dysplasia, sensorineural hearing loss, and distinctive facial features
MedGen UID:
355878
Concept ID:
C1864966
Disease or Syndrome
Deafness, autosomal recessive 51
MedGen UID:
355880
Concept ID:
C1864968
Disease or Syndrome
Spondylomegaepiphyseal dysplasia with upper limb mesomelia, punctate calcifications, and deafness
MedGen UID:
355893
Concept ID:
C1865022
Disease or Syndrome
Hystrix-like ichthyosis with deafness
MedGen UID:
355410
Concept ID:
C1865234
Disease or Syndrome
Hystrix-like ichthyosis with deafness (HID) is a disorder characterized by dry, scaly skin (ichthyosis) and hearing loss that is usually profound. Hystrix-like means resembling a porcupine; in this type of ichthyosis, the scales may be thick and spiky, giving the appearance of porcupine quills.Newborns with HID typically develop reddened skin. The skin abnormalities worsen over time, and the ichthyosis eventually covers most of the body, although the palms of the hands and soles of the feet are usually only mildly affected. Breaks in the skin may occur and in severe cases can lead to life-threatening infections. Affected individuals have an increased risk of developing a type of skin cancer called squamous cell carcinoma, which can also affect mucous membranes such as the inner lining of the mouth. People with HID may also have patchy hair loss caused by scarring on particular areas of skin.
Bartter syndrome type 4
MedGen UID:
355430
Concept ID:
C1865270
Disease or Syndrome
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal (or neonatal) forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, 607364) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Deafness, autosomal recessive 18
MedGen UID:
356389
Concept ID:
C1865870
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Otofacioosseous-gonadal syndrome
MedGen UID:
356416
Concept ID:
C1865988
Disease or Syndrome
Deafness, autosomal dominant 13
MedGen UID:
400917
Concept ID:
C1866095
Disease or Syndrome
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
Penttinen-Aula syndrome
MedGen UID:
400936
Concept ID:
C1866182
Disease or Syndrome
Penttinen syndrome is characterized by a prematurely aged appearance involving lipoatrophy and epidermal and dermal atrophy, as well as hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acroosteolysis (Johnston et al., 2015).
Peroxisome biogenesis disorder, complementation group R
MedGen UID:
356213
Concept ID:
C1866351
Disease or Syndrome
Peroxisome Biogenesis Disorder, Complementation Group R
MedGen UID:
356512
Concept ID:
C1866352
Disease or Syndrome
Spondyloepiphyseal dysplasia, myopia, and sensorineural deafness
MedGen UID:
401067
Concept ID:
C1866719
Disease or Syndrome
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 (wide bridge of the nose continuing to the forehead), microcephaly, high anterior hairline with prominent glabella, widely spaced eyes, epicanthus, highly arched eyebrows, short philtrum, downturned corners of the 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 90% 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%).
Brachydactyly type B2
MedGen UID:
409880
Concept ID:
C1969652
Disease or Syndrome
Brachydactyly type B2 (BDB2) is a subtype of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones, and partial cutaneous syndactyly.
Hamamy syndrome
MedGen UID:
370148
Concept ID:
C1970027
Disease or Syndrome
Xeroderma pigmentosum, complementation group b
MedGen UID:
373493
Concept ID:
C1970808
Disease or Syndrome
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
Phosphoribosylpyrophosphate synthetase superactivity
MedGen UID:
370358
Concept ID:
C1970827
Disease or Syndrome
Phosphoribosylpyrophosphate synthetase (PRS) superactivity is characterized by hyperuricemia and hyperuricosuria and is divided into a severe phenotype with infantile or early-childhood onset and a milder phenotype with late-juvenile or early-adult onset. Variable combinations of sensorineural hearing loss, hypotonia, and ataxia observed in the severe type are not usually present in the mild type. In the mild type, uric acid crystalluria or a urinary stone is commonly the first clinical finding, followed later by gouty arthritis if serum urate concentration is not controlled.
Stickler syndrome type 1
MedGen UID:
810955
Concept ID:
C2020284
Congenital Abnormality
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Charcot-Marie-Tooth disease type 2C
MedGen UID:
389170
Concept ID:
C2079540
Disease or Syndrome
Charcot-Marie-Tooth hereditary neuropathy type 2 (CMT2) is an axonal (non-demyelinating) peripheral neuropathy characterized by distal muscle weakness and atrophy, mild sensory loss, and normal or near-normal nerve conduction velocities. CMT2 is clinically similar to CMT1, although typically less severe. Peripheral nerves are not enlarged or hypertrophic. The subtypes of CMT2 are similar clinically and distinguished only by molecular genetic findings.
Familial cold autoinflammatory syndrome 2
MedGen UID:
435869
Concept ID:
C2673198
Disease or Syndrome
Familial cold autoinflammatory syndrome is a condition that causes episodes of fever, skin rash, and joint pain after exposure to cold temperatures. These episodes usually begin in infancy and occur throughout life.People with this condition usually experience symptoms after cold exposure of an hour or more, although in some individuals only a few minutes of exposure is required. Symptoms may be delayed for up to a few hours after the cold exposure. Episodes last an average of 12 hours, but may continue for up to 3 days.In people with familial cold autoinflammatory syndrome, the most common symptom that occurs during an episode is an itchy or burning rash. The rash usually begins on the face or extremities and spreads to the rest of the body. Occasionally swelling in the extremities may occur.In addition to the skin rash, episodes are characterized by fever, chills, and joint pain, most often affecting the hands, knees, and ankles. Redness in the whites of the eye (conjunctivitis), sweating, drowsiness, headache, thirst, and nausea may also occur during an episode of this disorder.
Deafness, autosomal recessive 1A
MedGen UID:
388720
Concept ID:
C2673759
Disease or Syndrome
Nonsyndromic hearing loss and deafness (DFNB1) is characterized by congenital non-progressive mild-to-profound sensorineural hearing impairment. No other associated medical findings are present.
Chromosome 10q26 deletion syndrome
MedGen UID:
436306
Concept ID:
C2674937
Disease or Syndrome
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract
MedGen UID:
436373
Concept ID:
C2675204
Disease or Syndrome
Chromosome 6pter-p24 deletion syndrome
MedGen UID:
393396
Concept ID:
C2675486
Disease or Syndrome
Deafness, congenital, with onychodystrophy, autosomal dominant
MedGen UID:
382676
Concept ID:
C2675730
Disease or Syndrome
The DDOD syndrome is characterized by autosomal dominant inheritance of congenital deafness and onychodystrophy. Conical, hypoplastic teeth is also a feature (Robinson et al., 1962). See also DOOR syndrome (220500), an autosomal recessive disorder, which includes congenital deafness, onychodystrophy, osteodystrophy, and mental retardation.
Deafness, autosomal dominant 3a
MedGen UID:
436512
Concept ID:
C2675750
Disease or Syndrome
Nonsyndromic hearing loss and deafness, DFNA3 is characterized by pre- or postlingual, mild-to-profound progressive high-frequency sensorineural hearing impairment. Affected individuals have no other associated medical findings.
2p15-16.1 microdeletion syndrome
MedGen UID:
390902
Concept ID:
C2675875
Disease or Syndrome
Chromosome 2p16.1-p15 deletion syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and variable but distinctive dysmorphic features, including microcephaly, bitemporal narrowing, smooth and long philtrum, hypertelorism, downslanting palpebral fissures, broad nasal root, thin upper lip, and high palate. Many patients have behavioral disorders, including autistic features, as well as structural brain abnormalities, such as pachygyria or hypoplastic corpus callosum. Those with deletions including the BCL11A gene (606557) also have persistence of fetal hemoglobin (HbF), which is asymptomatic and does not affected hematologic parameters or susceptibility to infection (summary by Funnell et al., 2015). Point mutation in the BCL11A gene causes intellectual developmental disorder with persistence of fetal hemoglobin (617101), which shows overlapping features. See also fetal hemoglobin quantitative trait locus-5 (HBFQTL5; 142335).
Jervell and Lange-Nielsen syndrome 2
MedGen UID:
394108
Concept ID:
C2676723
Disease or Syndrome
Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital profound bilateral sensorineural hearing loss and long QTc, usually greater than 500 msec. Prolongation of the QTc interval is associated with tachyarrhythmias, including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation, which may culminate in syncope or sudden death. Iron-deficient anemia and elevated levels of gastrin are also frequent features of JLNS. The classic presentation of JLNS is a deaf child who experiences syncopal episodes during periods of stress, exercise, or fright. Fifty percent of individuals with JLNS had cardiac events before age three years. More than half of untreated children with JLNS die prior to age 15 years.
Congenital disorder of glycosylation type 1N
MedGen UID:
383145
Concept ID:
C2677590
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065).
Hunter-MacDonald syndrome
MedGen UID:
383181
Concept ID:
C2677745
Disease or Syndrome
Mental retardation and microcephaly with pontine and cerebellar hypoplasia
MedGen UID:
437070
Concept ID:
C2677903
Disease or Syndrome
Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) is an X-linked disorder affecting females and characterized by severe intellectual disability, microcephaly, and variable degrees of pontocerebellar hypoplasia. Affected individuals have very poor psychomotor development, often without independent ambulation or speech, and axial hypotonia with or without hypertonia. Some may have sensorineural hearing loss or eye anomalies. Dysmorphic features include overall poor growth, severe microcephaly (-3.5 to -10 SD), broad nasal bridge and tip, large ears, long philtrum, micrognathia, and hypertelorism (summary by Moog et al., 2011).
Axenfeld-Rieger syndrome type 3
MedGen UID:
394534
Concept ID:
C2678503
Disease or Syndrome
Axenfeld-Rieger syndrome is primarily an eye disorder, although it can also affect other parts of the body. This condition is characterized by abnormalities of the front part of the eye, an area known as the anterior segment. For example, the colored part of the eye (the iris), may be thin or poorly developed. The iris normally has a single central hole, called the pupil, through which light enters the eye. People with Axenfeld-Rieger syndrome often have a pupil that is off-center (corectopia) or extra holes in the iris that can look like multiple pupils (polycoria). This condition can also cause abnormalities of the cornea, which is the clear front covering of the eye.About half of affected individuals develop glaucoma, a serious condition that increases pressure inside the eye. When glaucoma occurs with Axenfeld-Rieger syndrome, it most often develops in late childhood or adolescence, although it can occur as early as infancy. Glaucoma can cause vision loss or blindness.The signs and symptoms of Axenfeld-Rieger syndrome can also affect other parts of the body. Many affected individuals have distinctive facial features such as widely spaced eyes (hypertelorism); a flattened mid-face with a broad, flat nasal bridge; and a prominent forehead. The condition is also associated with dental abnormalities including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people with Axenfeld-Rieger syndrome have extra folds of skin around their belly button (redundant periumbilical skin). Other, less common features can include heart defects, the opening of the urethra on the underside of the penis (hypospadias), narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland that can result in slow growth.Researchers have described at least three types of Axenfeld-Rieger syndrome. The types, which are numbered 1 through 3, are distinguished by their genetic cause.
Perrault syndrome 3
MedGen UID:
473597
Concept ID:
C2681413
Gene or Genome
Perrault syndrome (PRLTS) is an autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) and premature ovarian failure (POF) secondary to ovarian dysgenesis. Affected males have SNHL but show normal pubertal development. A spectrum of additional clinical features, including cerebellar ataxia, learning disability, and peripheral neuropathy, have been described in some affected individuals (summary by Jenkinson et al., 2013). For a discussion of genetic heterogeneity of Perrault syndrome, see PRLTS1 (233400).
Waardenburg syndrome type 2E
MedGen UID:
398476
Concept ID:
C2700405
Disease or Syndrome
Waardenburg syndrome type 2 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (review by Read and Newton, 1997). Individuals with WS type 2E, which is caused by mutation in the SOX10 gene (602229), may have neurologic abnormalities, including mental impairment, myelination defects, and ataxia. Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580).
SeSAME syndrome
MedGen UID:
411243
Concept ID:
C2748572
Disease or Syndrome
Refsum disease, adult, 2
MedGen UID:
440765
Concept ID:
C2749346
Disease or Syndrome
Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria)
MedGen UID:
413170
Concept ID:
C2749864
Disease or Syndrome
SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized by onset of the following features in infancy or childhood (median age of onset 2 months; range of onset birth to 6 years): psychomotor retardation, hypotonia, dystonia, muscular atrophy, sensorineural hearing impairment, postnatal growth retardation, and feeding difficulties. Other less frequent features include distinctive facial features, contractures, kyphoscoliosis, gastroesophageal reflux, ptosis, choreoathetosis, ophthalmoplegia, and epilepsy (infantile spasms or generalized convulsions). The median survival is 20 years; approximately 30% of affected individuals succumb during childhood. Affected individuals may have hyperintensities in the basal ganglia, cerebral atrophy, and leukoencephalopathy on head MRI. Elevation of methylmalonic acid (MMA) in the urine and plasma is found in a vast majority of affected individuals, although at levels that are far below those typically seen in individuals with classic methylmalonic aciduria.
Deafness, autosomal recessive 79
MedGen UID:
413222
Concept ID:
C2750082
Disease or Syndrome
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).
Waardenburg syndrome type 4B
MedGen UID:
412961
Concept ID:
C2750457
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 4B is caused by mutation in the EDN3 gene (131242). 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).
Spastic paraplegia 44, autosomal recessive
MedGen UID:
413042
Concept ID:
C2750784
Disease or Syndrome
Bartter syndrome, type 4b
MedGen UID:
416521
Concept ID:
C2751312
Disease or Syndrome
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal (or neonatal) forms of Bartter syndrome (e.g., BARTS1, 601678) typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay
MedGen UID:
416525
Concept ID:
C2751320
Disease or Syndrome
Leukoencephalopathy, cystic, without megalencephaly
MedGen UID:
416646
Concept ID:
C2751843
Disease or Syndrome
RNAse T2-deficient leukoencephalopathy is a disorder that affects the brain. People with RNAse T2-deficient leukoencephalopathy have neurological problems that become apparent during infancy; the problems generally do not worsen over time (progress). Most affected individuals have severe intellectual disability; muscle stiffness (spasticity); and a delay in developing motor skills such as sitting, crawling, and walking. Some do not learn to walk, and most do not develop the ability to speak. Other neurological features that can occur in RNAse T2-deficient leukoencephalopathy include hearing loss caused by abnormalities in the inner ear (sensorineural deafness), seizures, involuntary writhing movements of the hands (athetosis), uncontrolled muscle tensing (dystonia), and involuntary eye movements (nystagmus). In addition to the neurological problems associated with this disorder, some affected individuals have unusual facial features sometimes described as a "doll-like face."The neurological problems in this disorder are caused by abnormalities in the brain. People with this condition have leukoencephalopathy, an abnormality of the brain's white matter that can be detected with medical imaging. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In people with RNAse T2-deficient leukoencephalopathy, myelin is not made in sufficient amounts during development, leading to patchy white matter abnormalities (lesions) in the brain. In addition, individuals with RNAse T2-deficient leukoencephalopathy may have cysts in regions of the brain called the temporal lobes and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. The white matter lesions are primarily concentrated around the cysts and the ventricles. An abnormally small head and brain size (microcephaly) often occurs in this disorder.
Stargardt macular degeneration absent or hypoplastic corpus callosum mental retardation and dysmorphic features
MedGen UID:
414494
Concept ID:
C2751864
Disease or Syndrome
Growth retardation, developmental delay, coarse facies, and early death
MedGen UID:
414158
Concept ID:
C2752001
Disease or Syndrome
Growth retardation, developmental delay, and facial dysmorphism (GDFD) is an autosomal recessive multiple congenital anomaly syndrome characterized by severe psychomotor retardation, poor overall growth, and dysmorphic facial features. Additional features may include cardiac malformations and deafness (summary by Daoud et al., 2016).
Leber congenital amaurosis 1
MedGen UID:
419026
Concept ID:
C2931258
Disease or Syndrome
Leber congenital amaurosis (LCA), a severe dystrophy of the retina, typically becomes evident in the first year of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia, and keratoconus. Visual acuity is rarely better than 20/400. A characteristic finding is Franceschetti's oculo-digital sign, comprising eye poking, pressing, and rubbing. The appearance of the fundus is extremely variable. While the retina may initially appear normal, a pigmentary retinopathy reminiscent of retinitis pigmentosa is frequently observed later in childhood. The electroretinogram (ERG) is characteristically "nondetectable" or severely subnormal.
Nephronophthisis-like nephropathy 1
MedGen UID:
461769
Concept ID:
C3150419
Disease or Syndrome
Nephronophthisis is an autosomal recessive cystic kidney disease characterized by onset of end-stage renal failure in the first 3 decades of life. The disorder is often associated with extrarenal manifestations, including liver fibrosis, retinal degeneration, and central nervous system abnormalities (summary by O'Toole et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (256100).
Congenital disorder of glycosylation type 1P
MedGen UID:
462263
Concept ID:
C3150913
Disease or Syndrome
LEOPARD syndrome 3
MedGen UID:
462321
Concept ID:
C3150971
Disease or Syndrome
Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. As the condition name suggests, Noonan syndrome with multiple lentigines is very similar to a condition called Noonan syndrome, and it can be difficult to tell the two disorders apart in early childhood. However, the features of these two conditions differ later in life. The characteristic features of Noonan syndrome with multiple lentigines include brown skin spots called lentigines that are similar to freckles, heart defects, widely spaced eyes (ocular hypertelorism), a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and short stature. These features vary, however, even among affected individuals in the same family. Not all individuals with Noonan syndrome with multiple lentigines have all the characteristic features of this condition.The lentigines seen in Noonan syndrome with multiple lentigines typically first appear in mid-childhood, mostly on the face, neck, and upper body. Affected individuals may have thousands of small dark brown skin spots by the time they reach puberty. Unlike freckles, the appearance of lentigines has nothing to do with sun exposure. In addition to lentigines, people with this condition may have lighter brown skin spots called café-au-lait spots. Café-au-lait spots tend to develop before the lentigines, appearing within the first year of life in most affected people.Of the people with Noonan syndrome with multiple lentigines who have heart defects, about 80 percent have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. The hypertrophic cardiomyopathy most often affects the lower left chamber of the heart (the left ventricle). Up to 20 percent of people with Noonan syndrome with multiple lentigines who have heart problems have a narrowing of the artery from the heart to the lungs (pulmonary stenosis).People with Noonan syndrome with multiple lentigines can have a distinctive facial appearance. In addition to ocular hypertelorism, affected individuals may have droopy eyelids (ptosis), thick lips, and low-set ears. Affected individuals also usually have an abnormal appearance of the chest; they either have pectus excavatum or pectus carinatum.At birth, people with Noonan syndrome with multiple lentigines are typically of normal weight and height, but in some, growth slows over time. This slow growth results in affected individuals being shorter than average, although less than half of people with Noonan syndrome with multiple lentigines have significantly short stature.Other signs and symptoms of Noonan syndrome with multiple lentigines include hearing loss caused by abnormalities in the inner ear (sensorineural deafness), mild intellectual disability, and extra folds of skin on the back of the neck. Affected males often have genital abnormalities, which can include undescended testes (cryptorchidism) and a urethra that opens on the underside of the penis (hypospadias). These abnormalities may reduce the ability to have biological children (decreased fertility). Females with Noonan syndrome with multiple lentigines may have poorly developed ovaries and delayed puberty.Noonan syndrome with multiple lentigines is one of a group of related conditions collectively known as RASopathies. These conditions all have similar signs and symptoms and are caused by changes in the same cell signaling pathway. In addition to Noonan syndrome with multiple lentigines, the RASopathies include Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Legius syndrome.
Deafness, autosomal recessive 61
MedGen UID:
462580
Concept ID:
C3151230
Disease or Syndrome
Hereditary sensory neuropathy type IE
MedGen UID:
481515
Concept ID:
C3279885
Disease or Syndrome
DNMT1-related dementia, deafness, and sensory neuropathy (HSAN IE) is a degenerative disorder of the central and peripheral nervous systems characterized by sensory impairment of the distal lower extremities, loss of sweating (sudomotor function) on the distal aspects of the upper and lower limbs, sensorineural hearing loss, and dementia. Affected persons are normal in their youth but begin to manifest progressive sensory neuropathy and moderate to severe progressive sensorineural deafness by age 20 to 35 years. The sensory alterations result in gait unsteadiness from sensory ataxia and mutilating ulcers and/or amputations of distal extremities in approximately 50% of affected persons. Dementia usually manifests by the fourth decade.
Deafness, autosomal dominant 64
MedGen UID:
481578
Concept ID:
C3279948
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).
Hypermethioninemia due to adenosine kinase deficiency
MedGen UID:
482011
Concept ID:
C3280381
Disease or Syndrome
Hypermethioninemia due to adenosine kinase deficiency is an autosomal recessive inborn error of metabolism characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy); homocysteine is typically normal (summary by Bjursell et al., 2011).
Infantile cerebellar-retinal degeneration
MedGen UID:
482822
Concept ID:
C3281192
Disease or Syndrome
Infantile cerebellar-retinal degeneration is a severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration (summary by Spiegel et al., 2012).
Peroxisome biogenesis disorder 5B
MedGen UID:
762202
Concept ID:
C3542026
Disease or Syndrome
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX2 gene have cells of complementation group 5 (CG5, equivalent to CG10 and CGF). For information on the history of PBD complementation groups, see 214100.
Coenzyme Q10 deficiency, primary, 6
MedGen UID:
766263
Concept ID:
C3553349
Disease or Syndrome
Primary coenzyme Q10 deficiency-6 is an autosomal recessive disorder characterized by onset in infancy of severe progressive nephrotic syndrome resulting in end-stage renal failure and sensorineural deafness. Renal biopsy usually shows focal segmental glomerulosclerosis (FSGS). Some patients may show a favorable response to oral coenzyme Q supplementation (summary by Heeringa et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278) and NPHS1 (256300).
Brown-Vialetto-Van Laere syndrome 2
MedGen UID:
766452
Concept ID:
C3553538
Disease or Syndrome
Brown-Vialetto-Van Laere syndrome-2 is an autosomal recessive progressive neurologic disorder characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting of the upper and lower limbs and axial muscles, resulting in respiratory insufficiency. Some patients may lose independent ambulation. Because it results from a defect in riboflavin metabolism, some patients may benefit from high-dose riboflavin supplementation (summary by Johnson et al., 2012; Foley et al., 2014). For discussion of genetic heterogeneity of Brown-Vialetto-Van Laere syndrome, see BVVLS1 (211530).
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome
MedGen UID:
766511
Concept ID:
C3553597
Disease or Syndrome
MEGDEL (3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like) syndrome is characterized in neonates by hypoglycemia and a sepsis-like clinical picture for which no infectious agent can be found. During the first year of life feeding problems, failure to thrive, and/or truncal hypotonia become evident; many infants experience (transient) liver involvement ranging from undulating transaminases to prolonged hyperbilirubinemia and near-fatal liver failure. By age two years progressive deafness, dystonia, and spasticity prevent further psychomotor development and/or result in loss of acquired skills. Affected children are completely dependent on care for all activities of daily living; speech is absent.
Peroxisome biogenesis disorder 4B
MedGen UID:
766851
Concept ID:
C3553937
Disease or Syndrome
Peroxisome biogenesis disorder-4B (PDB4B) includes the overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders (PBDs). The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX6 gene have cells of complementation group 4 (CG4, equivalent to CG6 and CGC). For information on the history of PBD complementation groups, see 214100.
Peroxisome biogenesis disorder 6B
MedGen UID:
766862
Concept ID:
C3553948
Disease or Syndrome
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood. Some patients with PEX10 mutations have a milder disorder characterized by childhood-onset cerebellar ataxia and neuropathy without mental retardation (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX10 gene have cells of complementation group 7 (CG7, equivalent to CGB). For information on the history of PBD complementation groups, see 214100.
Peroxisome biogenesis disorder 7B
MedGen UID:
766865
Concept ID:
C3553951
Disease or Syndrome
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX26 gene have cells of complementation group 8 (CG8, equivalent to CGA). For information on the history of PBD complementation groups, see 214100.
Peroxisome biogenesis disorder 8B
MedGen UID:
766874
Concept ID:
C3553960
Disease or Syndrome
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX16 gene have cells of complementation group 9 (CG9, equivalent to CGD). For information on the history of PBD complementation groups, see 214100.
CGR
MedGen UID:
766890
Concept ID:
C3553976
Finding
Perrault syndrome 2
MedGen UID:
767019
Concept ID:
C3554105
Disease or Syndrome
Perrault syndrome-2 is an autosomal recessive disorder characterized by sensorineural deafness in both males and females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile (summary by Pierce et al., 2011). For a discussion of genetic heterogeneity of Perrault syndrome, see PRLTS1 (233400).
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome
MedGen UID:
811623
Concept ID:
C3715192
Disease or Syndrome
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance, and metabolic abnormalities including insulin resistance and diabetes mellitus. Sensorineural deafness occurs late in the first or second decades of life (summary by Weedon et al., 2013).
Charcot-Marie-Tooth disease, X-linked dominant, 6
MedGen UID:
813032
Concept ID:
C3806702
Disease or Syndrome
Nephrotic syndrome, type 8
MedGen UID:
815283
Concept ID:
C3808953
Disease or Syndrome
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12
MedGen UID:
815294
Concept ID:
C3808964
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies. It is usually associated with delayed psychomotor development and shortened life expectancy. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as dystroglycanopathies (summary by Stevens et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 14
MedGen UID:
815546
Concept ID:
C3809216
Disease or Syndrome
Infantile liver failure syndrome 1
MedGen UID:
815852
Concept ID:
C3809522
Disease or Syndrome
Van Maldergem syndrome 2
MedGen UID:
816205
Concept ID:
C3809875
Disease or Syndrome
Van Maldergem syndrome is an autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia (summary by Cappello et al., 2013). For a discussion of genetic heterogeneity of Van Maldergem syndrome, see 601390.
Joubert syndrome 21
MedGen UID:
816542
Concept ID:
C3810212
Disease or Syndrome
Joubert syndrome is an autosomal recessive congenital condition characterized by a unique brainstem and cerebellar malformation comprising cerebellar vermis hypoplasia and/or dysplasia, elongated superior cerebellar peduncles, and deepened interpeduncular fossa, which together are recognized as the 'molar tooth sign' on brain MRI. The most common clinical features include delayed psychomotor development, hypotonia, abnormal respiratory patterns in the neonatal period, oculomotor apraxia, and cerebellar ataxia. Additional features may include retinal degeneration, cystic kidney, liver fibrosis, and polydactyly. It is caused by ciliary defects and is part of a spectrum of disorders known as 'ciliopathies' (summary by Akizu et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
DEAFNESS, AUTOSOMAL DOMINANT 50
MedGen UID:
854780
Concept ID:
C3888123
Disease or Syndrome
PGM3-CDG
MedGen UID:
862808
Concept ID:
C4014371
Disease or Syndrome
FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 2
MedGen UID:
863085
Concept ID:
C4014648
Disease or Syndrome
IMMUNODEFICIENCY 26 WITH OR WITHOUT NEUROLOGIC ABNORMALITIES
MedGen UID:
863270
Concept ID:
C4014833
Disease or Syndrome
CATARACTS, GROWTH HORMONE DEFICIENCY, SENSORY NEUROPATHY, SENSORINEURAL HEARING LOSS, AND SKELETAL DYSPLASIA
MedGen UID:
863379
Concept ID:
C4014942
Disease or Syndrome
DEAFNESS, AUTOSOMAL RECESSIVE 103
MedGen UID:
863487
Concept ID:
C4015050
Disease or Syndrome
SIDEROBLASTIC ANEMIA WITH B-CELL IMMUNODEFICIENCY, PERIODIC FEVERS, AND DEVELOPMENTAL DELAY
MedGen UID:
863609
Concept ID:
C4015172
Disease or Syndrome
ATAXIA, COMBINED CEREBELLAR AND PERIPHERAL, WITH HEARING LOSS AND DIABETES MELLITUS
MedGen UID:
863873
Concept ID:
C4015436
Disease or Syndrome
NEUROLOGIC, ENDOCRINE, AND PANCREATIC DISEASE, MULTISYSTEM, INFANTILE-ONSET
MedGen UID:
864165
Concept ID:
C4015728
Disease or Syndrome
DEAFNESS, AUTOSOMAL DOMINANT 40
MedGen UID:
896665
Concept ID:
C4084708
Disease or Syndrome
DEAFNESS, AUTOSOMAL DOMINANT 67
MedGen UID:
900413
Concept ID:
C4084712
Disease or Syndrome
RADIOULNAR SYNOSTOSIS WITH AMEGAKARYOCYTIC THROMBOCYTOPENIA 2
MedGen UID:
901732
Concept ID:
C4225221
Disease or Syndrome
CRANIOSYNOSTOSIS 6
MedGen UID:
904675
Concept ID:
C4225269
Disease or Syndrome
EPILEPSY, HEARING LOSS, AND MENTAL RETARDATION SYNDROME
MedGen UID:
895574
Concept ID:
C4225276
Disease or Syndrome
SHORT STATURE, MICROCEPHALY, AND ENDOCRINE DYSFUNCTION
MedGen UID:
895448
Concept ID:
C4225288
Disease or Syndrome
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 50
MedGen UID:
906893
Concept ID:
C4225319
Mental or Behavioral Dysfunction
ZIMMERMANN-LABAND SYNDROME 2
MedGen UID:
897567
Concept ID:
C4225321
Disease or Syndrome
SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 20
MedGen UID:
903867
Concept ID:
C4225355
Disease or Syndrome
ROBINOW SYNDROME, AUTOSOMAL DOMINANT 2
MedGen UID:
897039
Concept ID:
C4225363
Disease or Syndrome

Recent clinical studies

Etiology

Lin CS, Lin YS, Liu CF, Weng SF, Lin C, Lin BS
J Laryngol Otol 2016 Jan;130(1):42-9. Epub 2015 Nov 27 doi: 10.1017/S0022215115002960. PMID: 26611115
Fan W, Zhang W, Li J, Zhao X, Mella G, Lei P, Liu Y, Wang H, Cheng H, Shi H, Xu H
Otol Neurotol 2015 Dec;36(10):1622-7. doi: 10.1097/MAO.0000000000000892. PMID: 26595717Free PMC Article
Cho SW, Han KH, Jang HK, Chang SO, Jung H, Lee JH
Int J Audiol 2015;54(10):700-4. Epub 2015 May 21 doi: 10.3109/14992027.2015.1043148. PMID: 25997814
Chien CY, Tai SY, Wang LF, Hsi E, Chang NC, Wu MT, Ho KY
Otolaryngol Head Neck Surg 2015 Jul;153(1):105-11. Epub 2015 Mar 24 doi: 10.1177/0194599815575713. PMID: 25805640
Kvestad E, Lie KK, Eskild A, Engdahl B
Int J Pediatr Otorhinolaryngol 2014 Nov;78(11):1940-4. Epub 2014 Sep 1 doi: 10.1016/j.ijporl.2014.08.032. PMID: 25216808

Diagnosis

Hosokawa S, Sugiyama K, Takahashi G, Takebayashi S, Mineta H
J Laryngol Otol 2017 Jan;131(1):77-82. Epub 2016 Dec 5 doi: 10.1017/S0022215116009725. PMID: 27917721
Lin CS, Lin YS, Liu CF, Weng SF, Lin C, Lin BS
J Laryngol Otol 2016 Jan;130(1):42-9. Epub 2015 Nov 27 doi: 10.1017/S0022215115002960. PMID: 26611115
Fan W, Zhang W, Li J, Zhao X, Mella G, Lei P, Liu Y, Wang H, Cheng H, Shi H, Xu H
Otol Neurotol 2015 Dec;36(10):1622-7. doi: 10.1097/MAO.0000000000000892. PMID: 26595717Free PMC Article
Cho SW, Han KH, Jang HK, Chang SO, Jung H, Lee JH
Int J Audiol 2015;54(10):700-4. Epub 2015 May 21 doi: 10.3109/14992027.2015.1043148. PMID: 25997814
Kvestad E, Lie KK, Eskild A, Engdahl B
Int J Pediatr Otorhinolaryngol 2014 Nov;78(11):1940-4. Epub 2014 Sep 1 doi: 10.1016/j.ijporl.2014.08.032. PMID: 25216808

Therapy

Van Der Wal AW, Van Ooij PJ, De Ru JA
J Laryngol Otol 2016 Nov;130(11):1039-1047. Epub 2016 Oct 17 doi: 10.1017/S0022215116009075. PMID: 27748209
Heywood RL, Ifeacho SN, Narula AA
J Laryngol Otol 2016 Jun;130(6):532-5. Epub 2016 Apr 18 doi: 10.1017/S0022215116001110. PMID: 27087111
Bednar MM, DeMartinis N, Banerjee A, Bowditch S, Gaudreault F, Zumpano L, Lin FR
JAMA Otolaryngol Head Neck Surg 2015 Jul;141(7):607-13. doi: 10.1001/jamaoto.2015.0791. PMID: 25997115
Maeda Y, Kataoka Y, Sugaya A, Kariya S, Kobayashi K, Nishizaki K
Auris Nasus Larynx 2015 Jun;42(3):249-53. Epub 2014 Nov 28 doi: 10.1016/j.anl.2014.11.002. PMID: 25440412
Talaat HS, Metwaly MA, Khafagy AH, Abdelraouf HR
Int J Pediatr Otorhinolaryngol 2014 Jan;78(1):46-9. Epub 2013 Oct 30 doi: 10.1016/j.ijporl.2013.10.016. PMID: 24246243

Prognosis

Hosokawa S, Sugiyama K, Takahashi G, Takebayashi S, Mineta H
J Laryngol Otol 2017 Jan;131(1):77-82. Epub 2016 Dec 5 doi: 10.1017/S0022215116009725. PMID: 27917721
Heywood RL, Ifeacho SN, Narula AA
J Laryngol Otol 2016 Jun;130(6):532-5. Epub 2016 Apr 18 doi: 10.1017/S0022215116001110. PMID: 27087111
Cho SW, Han KH, Jang HK, Chang SO, Jung H, Lee JH
Int J Audiol 2015;54(10):700-4. Epub 2015 May 21 doi: 10.3109/14992027.2015.1043148. PMID: 25997814
Chien CY, Tai SY, Wang LF, Hsi E, Chang NC, Wu MT, Ho KY
Otolaryngol Head Neck Surg 2015 Jul;153(1):105-11. Epub 2015 Mar 24 doi: 10.1177/0194599815575713. PMID: 25805640
El-Badry MM, Hamdy NA, Sobhy S, Gamal R
Int J Pediatr Otorhinolaryngol 2014 Apr;78(4):623-30. Epub 2014 Jan 23 doi: 10.1016/j.ijporl.2014.01.018. PMID: 24552617

Clinical prediction guides

Casella G, Corbetta D, Zolezzi M, Di Bella C, Villanacci V, Salemme M, Milanesi U, Antonelli E, Baldini V, Bassotti G
Tech Coloproctol 2015 Dec;19(12):729-31. Epub 2015 Aug 18 doi: 10.1007/s10151-015-1349-7. PMID: 26280882
Cho SW, Han KH, Jang HK, Chang SO, Jung H, Lee JH
Int J Audiol 2015;54(10):700-4. Epub 2015 May 21 doi: 10.3109/14992027.2015.1043148. PMID: 25997814
Bednar MM, DeMartinis N, Banerjee A, Bowditch S, Gaudreault F, Zumpano L, Lin FR
JAMA Otolaryngol Head Neck Surg 2015 Jul;141(7):607-13. doi: 10.1001/jamaoto.2015.0791. PMID: 25997115
Tanigawa T, Shibata R, Tanaka H, Gosho M, Katahira N, Horibe Y, Nakao Y, Ueda H
J Laryngol Otol 2015 Jan;129(1):11-5. Epub 2014 Dec 8 doi: 10.1017/S0022215114003028. PMID: 25482388
Kvestad E, Lie KK, Eskild A, Engdahl B
Int J Pediatr Otorhinolaryngol 2014 Nov;78(11):1940-4. Epub 2014 Sep 1 doi: 10.1016/j.ijporl.2014.08.032. PMID: 25216808

Recent systematic reviews

Kyle ME, Wang JC, Shin JJ
Otolaryngol Head Neck Surg 2015 Jan;152(1):23-41. Epub 2014 Oct 30 doi: 10.1177/0194599814553930. PMID: 25358343Free PMC Article
Su CX, Yan LJ, Lewith G, Liu JP
Clin Otolaryngol 2013 Dec;38(6):455-73. doi: 10.1111/coa.12198. PMID: 24209508
Peeters N, van der Kolk BY, Thijsen SF, Colnot DR
Otol Neurotol 2013 Jul;34(5):832-7. doi: 10.1097/MAO.0b013e31827c9f93. PMID: 23303170
Mujica-Mota M, Waissbluth S, Daniel SJ
Head Neck 2013 Nov;35(11):1662-8. Epub 2012 Dec 22 doi: 10.1002/hed.23201. PMID: 23280686
Chau JK, Cho JJ, Fritz DK
Otolaryngol Clin North Am 2012 Oct;45(5):941-58. Epub 2012 Jul 26 doi: 10.1016/j.otc.2012.06.002. PMID: 22980677

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