Monogenic hearing loss

Gene: TBC1D24

Comment on list classification: Changed from Red to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association

Created: 21 Nov 2018, 1:28 p.m.

Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green

Created: 21 Nov 2018, 1:26 p.m.

Comment on phenotypes: Added phenotypes that indicate relevance to inclusion on the Hearing loss panel from OMIM. Removed: Myoclonic epilepsy, infantile, familial, 605021;Myoclonicepilepsy,infantile,familial,605021Epilepticencephalopathy,earlyinfantile,16,615338

Created: 21 Nov 2018, 1:24 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
#220500:DOOR syndrome[MicrocephalyNarrow bifrontal diameter; Coarse faciesLong philtrum; Deafness, sensorineural, profoundLow-set ears; Optic atrophyBlindnessHigh myopiaCataracts; Broad nasal bridgeLarge noseBulbous nasal tipAnteverted nares; Thick, everted lower lipDownturned corners of the mouthHigh-arched palate; Congenital heart defects (less common); Cystic renal dysplasia (less common)Renal aplasia (less common); Small or absent distal phalangesTriphalangeal thumbs; Small or absent distal phalanges; Small or absent nails on the hands and feet; Mental retardationHypotoniaSeizuresCerebral atrophyDilated ventriclesDandy-Walker malformation (rare); Peripheral polyneuropathyHyporeflexia; Increased serum and urinary 2-oxoglutarate]; #605021:Myoclonic epilepsy, infantile, familial[Delayed motor and speech development, mild (1 family)Myoclonic seizures, frequent, long-lasting (many hours)Focal seizuresFebrile seizuresGeneralized tonic-clonic seizuresIctal EEG with bisynchronous spike wavesIntellectual disabilities (in 1 family)Ataxia, (1 family)Dysarthria, mild (1 family)Brain MRI shows abnormal cortical thickening in the anteromesial frontal areas (1 family)]; #614617:Deafness , autosomal recessive 86[Deafness, profound, affects all frequencies]; #615338:Epileptic encephalopathy, early infantile, 16[Microcephaly, acquired (in some patients); Loss of eye contactVisual lossOptic atrophy (rare); Hypotonia, severe; Epileptic encephalopathySeizures, tonic, clonic, focalProlonged seizuresStatus epilepticusMigrating clonic jerks (in some patients)MyoclonusPsychomotor regressionPsychomotor retardation, severeHypotoniaDystoniaHemiparesisExtrapyramidal signsHemiparesisMultifocal spikes and progressive slowing of background activity seen on EEGProgressive cerebral atrophy seen on MRIDelayed myelination]; #616044:Deafness, autosomal dominant 65[Hearing loss, progressive, (high frequency loss at first progressing to loss of all frequencies)Absent or abnormal otoacoustic emissions]

Publications

• PMID:10574461
• 10741954
• 20727515
• 20797691
• 21087195
• 22211675
• 23343562
• 23526554
• 24291220
• 24387994
• 24729539
• 24729547