Monogenic hearing loss

Gene: HSD17B4

New review confirms gene status and mode of inheritance; no changes required.

Created: 11 Oct 2018, 1:48 p.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#233400:Perrault syndrome 1[Growth retardation; Hearing loss, sensorineural; NystagmusLimited extraocular movements; High-arched palate; Immature genitalia; Ovarian dysgenesisSmall ovariesLack of ovariesStreak gonads; Scoliosis; Pes cavusPes equinovarus; Weakness of the lower limbs; Delayed motor development (in some patients)Cognitive impairment (in some patients)Ataxic gait (in some patients)Spastic diplegia (in some patients)Dysarthria (in some patients)Cognitive impairment (in some patients)Cerebellar atrophy (in some patients); Sensorimotor demyelinating or axonal peripheral neuropathy (in some patients)Hyporeflexia (in some patients)Areflexia (in some patients); Amenorrhea, primaryIncreased gonadotropin levelsLow estradiol; Decreased beta-oxidation of pristanic acid]; #261515:D-bifunctional protein deficiency[Failure to thrive (44% of patients); MacrocephalyScaphocephalyLarge fontanellesDelayed closure of the fontanelles; Facial dysmorphism (68%)Frontal bossingHigh foreheadMicrognathiaRetrognathiaLong philtrum; Low-set earsLoss of hearing (45%); Upslanting palpebral fissuresEpicanthal foldsHypertelorismVisual impairment (55%)NystagmusStrabismusFailure to fixate on objectsLoss of vision (34%)Abolished electroretinogram (ERG) (76%); Depressed nasal bridge; High-arched palate; Funnel chestLong, small thorax; Abnormal liver function (26%)Hepatomegaly (43%)Histology shows normal numbers of peroxisomes (84%)Abnormal peroxisomes (53%)Absence of peroxisomes (16%)Cholestasis (9%)Steatosis (22%)Fibrosis (22%)Hemosiderosis (13%)Proliferation of bile canaliculi (9%); Poor feeding; Renal cysts (33%)Adrenal cortex atrophy (42%); Generalized osteopeniaDelayed bone maturationCalcific stippling; Claw hands; Talipes equinovarusHammertoes; Decreased muscle mass; Hypotonia, neonatal (> 90%)Seizures (> 90%)Delayed psychomotor development, severe (> 90%)Polymicrogyria (64%)Ventricular dilatation (29%)White matter dysmyelination/demyelination (71%)Neocortical dysplasia (27%)Hypoplastic/atrophic corpus callosum (55%)Heterotopic neurons in the white matter (36%)Generalized cerebral hypoplasia/atrophy (45%)Cerebellar hypoplasia/atrophy (27%)Gliosis (27%); Delayed peripheral nerve motor conduction velocities (67%); Adrenocortical insufficiency (uncommon); PolyhydramniosFetal ascites; Increased plasma levels of very long-chain fatty acids (VLCFA)Increased plasma levels of bile acid intermediatesDecreased peroxisomal fatty acid beta-oxidationDecreased or absent D-bifunctional protein activity and proteinNormal serum plasmalogen]

Publications

• PMID:10199776
• 10400999
• 10748062
• 11743515
• 11992265
• 15216544
• 16385454
• 180535
• 20673864
• 23181892
• 24553428
• 2868085
• 2882519
• 2921319
• 4061497
• 7487879
• 8279468
• 8621399
• 8902629
• 8938456
• 9089413
• 9133619
• 9197465
• 9345094
• 9482850
• 9880674
• 9915948

Comment when marking as ready: Expert review and OMIM confirmed

Created: 29 Jan 2016, 3:36 p.m.

Green List (high evidence)

can present as non-syndromic HL

Created: 19 Oct 2015, 7:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal