Klinische FragestellungHörverlust, autosomal rezessiv; Differentialdiagnose

NGS +

[Sanger]

Mehr als 50% des prä-lingualen Hörverlusts ist genetisch bedingt, ca. 90% dieser häufigsten sensorischen Defizite werden autosomal rezessiv vererbt. Einige Formen der genetisch bedingten Taubheit können an den damit verbundenen Syndrom-Merkmalen differenziert werden, aber in den meisten Fällen ist der Hörverlust der einzige Befund und wird als nicht-syndromische Taubheit bezeichnet. Bis heute wurden mehrere Tausend Mutationen in >130 Genen bei Patienten mit autosomal rezessivem nicht-syndromischem Hörverlust identifiziert. Die Mutationen in den GJB2 und GJB6 Genen sind in vielen Populationen häufige Ursachen für Hörverlust. Besonders bemerkenswert sind die extreme Lokus- und Allel-Heterogenität sowie die unterschiedlichen Spektren der Gene und Mutationen in verschiedenen Populationen. Genetisch bedingte Hörverluste treten in jedem Lebensalter auf, wenngleich monogen-bedingte Formen zumeist bereits prä-lingual symptomatisch sind. Die diagnostische Ausbeute beträgt je nach untersuchter Population ca. 40%. Ein unauffälliger genetischer Befund bedeutet daher keinen Ausschluss der klinischen Verdachtsdiagnose.

(Basisdiagnostik-Gene: ###; zusätzliche Gene: ###)

Referenz: https://www.ncbi.nlm.nih.gov/books/NBK1434/

• Alias: AR isolated neurosensory deafness type DFNB
• Alias: AR isolated sensorineural deafness type DFNB
• Alias: AR non-syndromic neurosensory deafness type DFNB
• Alias: AR non-syndromic sensorineural deafness type DFNB
• Alias: Deafness, hearing impairment
• Alias: Schwerhörigkeit
• Alias: Taubheit, autosomal rezessiv
• Allelic: Bart-Pumphrey syndrome (GJB2)
• Allelic: Charcot-Marie-Tooth disease, DI C (YARS1)
• Allelic: Combined oxidative phosphorylation deficiency 24 (NARS2)
• Allelic: Deafness, AD 11 (MYO7A)
• Allelic: Deafness, AD 3A (GJB2)
• Allelic: Deafness, AD 3B (GJB6)
• Allelic: Deafness, AD 78 (SLC12A2)
• Allelic: Deafness, AD 8/12 (TECTA)
• Allelic: Deafness, AD 81 (ELMOD3)
• Allelic: Deafness, AR (GJB3)
• Allelic: Deafness, AR 4, with enlarged vestibular aqueduct (SLC26A4)
• Allelic: Deafness, AR 88 (ELMOD3)
• Allelic: Delpire-McNeill syndrome (SLC12A2)
• Allelic: Ectodermal dysplasia 2, Clouston type (GJB6)
• Allelic: Epiphyseal dysplasia, multiple, 2 (COL9A2)
• Allelic: Epiphyseal dysplasia, multiple, 3, with/-out myopathy (COL9A3)
• Allelic: Epiphyseal dysplasia, multiple, 6 (COL9A1)
• Allelic: Fazio-Londe disease (SLC52A3)
• Allelic: Hirschsprung disease, susceptibility to, 4 (EDN3)
• Allelic: Hystrix-like ichthyosis with deafness (GJB2)
• Allelic: Intervertebral disc disease, susceptibility to (COL9A3)
• Allelic: Keratitis-ichthyosis-deafness syndrome (GJB2)
• Allelic: Keratoderma, palmoplantar, with deafness (GJB2)
• Allelic: Long QT syndrome 5 (KCNE1)
• Allelic: Nephronophthisis 19 (DCDC2)
• Allelic: Osteofibrous dysplasia, susceptibility to (MET)
• Allelic: Sclerosing cholangitis, neonatal (DCDC2)
• Allelic: Very Early Onset Inflammatory Bowel Disease (STXBP3)
• Allelic: Vohwinkel syndrome (GJB2)
• 3-methylglutaconic aciduria, deafness, encephalopathy, Leigh-like syndrome (SERAC1)
• Alias: AR non-syndromic neurosensory hearing loss type DFNB
• Alias: AR non-syndromic sensorineural hearing loss type DFNB
• Auditory neuropathy + optic atrophy (FDXR)
• Brown-Vialetto-Van Laere syndrome 1 (SLC52A3)
• Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• Cochlea malformations [panelapp] (FOXF2)
• Coenzyme Q10 deficiency, primary, 2 (PDSS1)
• Cone-rod dystrophy + hearing loss 2 (CEP250)
• Cone-rod dystrophy and hearing loss (CEP78)
• Deafness + myopia (SLITRK6)
• Deafness [panelapp] (SPATC1L)
• Deafness, AR 100 (PPIP5K2)
• Deafness, AR 103 (CLIC5)
• Deafness, AR 104 (RIPOR2)
• Deafness, AR 106 (EPS8L2)
• Deafness, AR 107 (WBP2)
• Deafness, AR 108 (ROR1)
• Deafness, AR 109 (ESRP1)
• Deafness, AR 110 (COCH)
• Deafness, AR 111 (MPZL2)
• Deafness, AR 112 (BDP1)
• Deafness, AR 113 (CEACAM16)
• Deafness, AR 114 (GRAP)
• Deafness, AR 115 (SPNS2)
• Deafness, AR 116 (CLDN9)
• Deafness, AR 117 (CLRN2)
• Deafness, AR 119 (SPATA5L1)
• Deafness, AR 12, modifier of (ATP2B2)
• Deafness, AR 16 (STRC)
• Deafness, AR 1A (GJB2)
• Deafness, AR 1B (GJB6)
• Deafness, AR 2 (MYO7A)
• Deafness, AR 21 (TECTA)
• Deafness, AR 22 (OTOA)
• Deafness, AR 25 (GRXCR2)
• Deafness, AR 26 (GAB1)
• Deafness, AR 32, with/-out immotile sperm (CDC14A)
• Deafness, AR 36 (ESPN)
• Deafness, AR 37 (MYO6)
• Deafness, AR 39 (HGF)
• Deafness, AR 44 (ADCY1)
• Deafness, AR 53 (COL11A2)
• Deafness, AR 59 (PJVK)
• Deafness, AR 66 (DCDC2)
• Deafness, AR 68 (S1PR2)
• Deafness, AR 7 (TMC1)
• Deafness, AR 86 (TBC1D24)
• Deafness, AR 91 (SERPINB6)
• Deafness, AR 94 (NARS2)
• Deafness, AR 97 (MET)
• Deafness, AR 99 (TMEM132E)
• Deafness, DIG GJB2/GJB6 (GJB2/GJB6)
• Enlarged vestibular aqueduct (FOXI1)
• Epilepsy, hearing loss + mental retardation syndrome (SPATA5)
• Hypokalemic tubulopathy + deafness (KCNJ16)
• Incomplete partition type I anomaly of the cochlea [panelapp] (FOXF2)
• Infantile-onset multisystem neurologic, endocrine + pancreatic disease 2 (YARS1)
• Jervell + Lange-Nielsen syndrome 2 (KCNE1)
• Kilquist syndrome (SLC12A2)
• Leukodystrophy, hypomyelinating, 23 + ataxia, deafness, liver dysfunction, dil. cardiomyop. (RNF220)
• MEDNIK syndrome (AP1S1)
• Muscular dystrophy, congenital hearing loss + ovarian insufficiency syndrome (GGPS1)
• Nephrotic syndrome, type 14 (SGPL1)
• Neurodevelopmental disorder with hearing loss + spasticity (SPATA5L1)
• Neurodevelopmental disorder with hypotonia, neuropathy + deafness (SPTBN4)
• Pendred syndrome (SLC26A4)
• Perrault syndrome 2 (HARS2)
• Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa + cataract (ABDH12)
• Profound sensorineural hearing loss [panelapp] (FOXF2)
• Sensorineural hearing loss (STXBP3)
• Stickler syndrome [MONDO:0019354] (COL9A3)
• Stickler syndrome, type IV (COL9A1)
• Stickler syndrome, type V (COL9A2)
• Usher syndrome, type 1B (MYO7A)
• Usher syndrome, type 2C (ADGRV1)
• Usher syndrome, type 2C, GPR98/PDZD7 digenic (ADGRV1)
• Vertebral, cardiac, renal + limb defects syndrome 1 (HAAO)
• Waardenburg syndrome, type 4B (EDN3)
• Wolfram syndrome 2 (CISD2)