Monogenic hearing loss

Gene: GJA1

Red List (low evidence)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
#104100:Palmoplantar keratoderma with congenital alopecia[Palmoplantar keratosisPigmentary changes on the shins (1 patient)Focal palmoplantar keratoderma on weight-bearing areasTransgradient palmoplantar keratoderma on dorsal hands and feetHyperkeratosis of perianal areas, auricles, knuckles, knees, and anklesKeratosis pilaris of trunk and extremitiesSpiky hyperkeratotic lesions on ankles, elbows, and popliteal fossae; OrthohyperkeratosisFollicular pluggingPerivascular lymphocytic infiltration in papillary dermis; Leukonychia totalisDystrophic nails, mild; Alopecia, congenitalSparse, short, brittle hair on scalpScant body hairMultiple pits on electron microscopyCuticular weathering on electron microscopy]; #133200:Erythrokeratodermia variabilis et progressiva[Hyperkeratosis, generalizedLocalized symmetric fixed, yellow- or red-brown hyperkeratotic plaques (extensor surface of extremities, buttocks, and lateral trunk)Palmoplantar keratoderma, patchy (> 50%)Transient, migratory sharply outlined erythema (in some patients)Darkening of periorificial areas; PapillomatosisAcanthosisHypergranulosisCompact orthohyperkeratosis with retained nucleiFollicular plugging in less affected areas; Enlarged porcelain-white lunulae]; #164200:Oculodentodigital dysplasia[Microcephaly; Dysplastic ears (in some patients)Hearing loss, conductive; MicrocorneaMicrophthalmiaShort palpebral fissuresEpicanthal foldsGlaucomaCataractIris anomalies; Small naresThin hypoplastic alae nasiNarrow nasal bridgeThin anteverted naresProminent columnella; Cleft lipCleft palateBroad alveolar ridges; Enamel hypoplasiaSelective tooth agenesisMicrodontiaPremature loss of teethDental cariesTaurodontism (reported in 1 patient); Endocardial cushion defects (uncommon)Atrial septal defect (uncommon)Ventral septal defect (uncommon)Cardiac conduction defects (uncommon); Bowel dysfunction (in some cases); Neurogenic bladder (in some patients); Skull hyperostosis; Vertebral hyperostosis; Hip dislocation; Broad tubular bonesCubitus valgus; Syndactyly of 4th - 5th fingersShort middle phalanx of the 5th fingerFifth finger camptodactylyMidphalangeal hypoplasiaClinodactyly; Syndactyly of 3rd - 4th toes; Diffuse yellow-orange non-epidermolytic hyperkeratosis on palms and soles (palmoplantar keratoderma); Brittle nails; Fine, dry hairSparse, slow-growing hair; Lymphedema of lower limbs (in some patients); Mental retardation (rare)Hyperactive deep tendon reflexesParaparesisQuadriparesisAtaxiaSpasticityDysarthriaSeizuresNeurogenic bladderBasal ganglia calcificationCerebral white matter abnormalities]; #186100:Syndactyly, type III[Syndactyly; Complete bilateral syndactyly between 4th and 5th fingers; Occasional fusion of distal phalanges; Short 5th finger with absent/rudimentary middle phalanx; Unaffected feet]; #218400:Craniometaphyseal dysplasia, autosomal recessive[Macrocephaly; Coarse facial features; Mixed hearing loss; Dystopia canthorumHypertelorismOptic atrophy; Broad nasal bridgeBony paranasal bossing; Widened alveolar ridges; Delayed eruption of permanent teeth; Nasal obstruction leading to mouth breathing; Mild anterior rib widening; Hyperostosis of cranial vaultEnlarged mandibleHyperostosis of facial bonesObliteration of paranasal sinuses and mastoid; Gene valgumDense diaphysesMetaphyseal flaringClub-shaped distal femoraHumeri, radii, ulnae bowing; Metacarpal sclerosisPhalangeal sclerosis; Normal intelligenceFacial palsy]; #241550:Hypoplastic left heart syndrome 1[Hypoplastic left heart; Usually fatal in infancy]; #257850:Oculodentodigital dysplasia, autosomal recessive[Short stature; Failure to thrive; Brachycephaly; Frontal bossingLong philtrumMaxillary hypoplasiaMicrognathia; Low-set earsProminent ear lobes; Hypoplastic eyebrowsSparse eyelashesTelecanthusShort palpebral fissuresDownslanting palpebral fissuresMyopiaMicrophthalmiaMicrocorneaCataractPersistent pupillary membrane; Long narrow noseHypoplastic nasal alae; Small mouthThin lips; Delayed tooth eruptionHypoplastic teethMalocclusionProminent upper incisorsDental crowding; Delayed bone age; Large fontanelles at birthWidely separated sutures at birthBrachycephalyFrontal bossing; Small handsVariable cutaneous syndactyly involving fingers 3, 4, and 5Fifth-finger clinodactylyEnlarged distal interphalangeal joints; Small feetEnlarged distal interphalangeal joints; Sparse fine hair; Hypotonia at birthPsychomotor retardation, mildAbnormal gray and white matter differentiation in frontal, occipital, and cerebellar regions on CT scan; Low insulin-like growth factor-I (IGF1) levelsAbnormal growth hormone () response to stimulus; Caused by mutation in the alpha-1 gap junction protein gene (GJA1,)]; #600309:Atrioventricular septal defect 3[Atrioventricular septal defect (AVSD); Ostium primum atrial septal defect; Ventricular septum inlet defect; Tricuspid and mitral valves are replaced by a single inlet valve; Congestive failure; Lower left sternal thrill and pansystolic murmur; Poorly localized midsystolic murmur; Cyanosis; Pulmonary hypertension; Characteristic feature of Down syndrome; Superior axis and first-degree heart block on EKG; Chararacteristic 4-chamber echocardiogram]

Publications

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