IllnessHearig loss, extended panel incl. syndromes; differential diagnosis

NGS +

Hereditary hearing loss and deafness can be considered as syndromal or non-syndromal. More than 400 genetic syndromes have been described that include hearing loss. Non-syndromal hearing loss is not associated with visible abnormalities of the outer ear or related medical problems; however, it may be associated with abnormalities of the middle ear and/or inner ear. The causes of non-syndromic hearing loss are complex. Approximately 80% of prelingual deafness is genetic involving >100 genes, most commonly autosomal recessive and non-syndromic, 20% autosomal dominant and 1%-1.5% X-chromosomal or mitochondrial. The most common causes of severe autosomal recessive non-syndromic hearing loss are mutations in the GJB2 gene in most populations. The most common cause of mild to moderate autosomal recessive hearing loss is an STRC mutation, albeit with significant ethnic differences. In post-lingual non-syndromic hearing loss, most reported families show an autosomal dominant inheritance pattern. Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity, underscoring the importance of using multigene sequencing panels for genetic diagnosis. The DNA-diagnostic yield rarely exceeds 33%, which does not exclude the clinical diagnosis molecular genetically.

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

• Alias Hearing loss, deafness
• Alias: Deafness, AD
• Alias: Lethal short-limbed platyspondylic dwarfism, San Diego type
• Alias: Platyspondylic lethal skeletal dysplasia, San Diego type
• Alias: Schwerhörigkeit, Hörstörungen, Taubheit
• Alias: Thanatophoric dwarfism
• Alias: Thanatophoric dwarfism-cloverleaf
• Alias: Thanatophoric dwarfism-cloverleaf skull syndrome
• Allelic: Achondroplasia (FGFR3)
• Allelic: Anterior segment anomalies with/-out cataract (EYA1)
• Allelic: Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Allelic: Aplasia of lacrimal + salivary glands (FGF10)
• Allelic: Atrial fibrillation, familial, 3 (KCNQ1)
• Allelic: Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Allelic: Behr syndrome (OPA1)
• Allelic: Bent bone dysplasia syndrome (FGFR2)
• Allelic: Cardiomyopathy, dilated, 1J (EYA4)
• Allelic: Cataract 41 (WFS1)
• Allelic: Charcot-Marie-Tooth disease, AR intermediate, B (KARS1)
• Allelic: Charcot-Marie-Tooth disease, XLR, 5 (PRPS1)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2Z (MORC2)
• Allelic: Charcot-Marie-Tooth disease, dominant intermediate C (YARS)
• Allelic: Charcot-Marie-Tooth disease, type 1A (PMP22)
• Allelic: Combined oxidative phosphorylation deficiency 13 (PNPT1)
• Allelic: Corneal dystrophy, Fuchs endothelial, 4 (SLC4A11)
• Allelic: Corneal endothelial dystrophy, AR (SLC4A11)
• Allelic: Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Allelic: Craniosynostosis nonspecific (FGFR2)
• Allelic: Crouzon syndrome (FGFR2)
• Allelic: Crouzon syndrome [craniofacial dysostosis] with acanthosis nigricans (FGFR3)
• Allelic: Delpire-McNeill syndrome (SLC12A2)
• Allelic: Dentin dysplasia, type II (DSPP)
• Allelic: Dentinogenesis imperfecta, Shields type II (DSPP)
• Allelic: Dentinogenesis imperfecta, Shields type III (DSPP)
• Allelic: Developmental + epileptic encephalopathy 16 (TBC1D24)
• Allelic: Developmental + epileptic encephalopathy 81 ((DMXL2)
• Allelic: Diabetes mellitus, noninsulin-dependent, association with (WFS1)
• Allelic: Ectodermal dysplasia 2, Clouston type (GJB6)
• Allelic: Epilepsy, rolandic, with proxysmal exercise-induce dystonia + writer's cramp (TBC1D24)
• Allelic: Epiphyseal dysplasia, multiple, 2 (COL9A2)
• Allelic: Epiphyseal dysplasia, multiple, 3, with/-out myopathy (COL9A3)
• Allelic: Epiphyseal dysplasia, multiple, 6 (COL9A1)
• Allelic: Erythrokeratodermia variabilis et progressiva 1 (GJB3)
• Allelic: Febrile seizures, familial, 4 (ADGRV1)
• Allelic: Fibrochondrogenesis 1 (COL11A1)
• Allelic: Fibrochondrogenesis 2 (COL11A2)
• Allelic: GRACILE syndrome (BCS1L)
• Allelic: Gastric cancer, somatic (FGFR2)
• Allelic: Gastrointestinal stromal tumor, familial 606764 AD, IC 3
• Allelic: Glaucoma, normal tension, susceptibility to (OPA1)
• Allelic: Glomerulosclerosis, focal segmental, 7 (PAX2)
• Allelic: Gout, PRPS-related (PRPS1)
• Allelic: Hirschsprung disease, susceptibility to, 2 (EDNRB)
• Allelic: Hirschsprung disease, susceptibility to, 4 (EDN3)
• Allelic: Hydrops, lactic acidosis + sideroblastic anemia (LARS2)
• Allelic: Hyperpigmentation with/-out hypopigmentation (KITLG)
• Allelic: Hypochondroplasia (FGFR3)
• Allelic: Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Allelic: Intervertebral disc disease, susceptibility to (COL9A3)
• Allelic: Jackson-Weiss syndrome (FGFR2)
• Allelic: Kniest dysplasia (COL2A1)
• Allelic: Long QT syndrome 1 (KCNQ1)
• Allelic: Long QT syndrome 1, acquired, susceptibility to (KCNQ1)
• Allelic: Long QT syndrome 5 (KCNE1)
• Allelic: Lumbar disc herniation, susceptibility to (COL11A1)
• Allelic: Mastocytosis, cutaneous (KIT)
• Allelic: Melanoma, cutaneous malignant, susceptibility to, 8 (MITF)
• Allelic: Meningioma (MN1)
• Allelic: Migraine, resistance to (EDNRA)
• Allelic: Mitochondrial DNA depletion syndrome 14, encephalocardiomyopathic type (OPA1)
• Allelic: Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
• Allelic: Muenke syndrome (FGFR3)
• Allelic: Myoclonic epilepsy, infantile, familial (TBC1D24)
• Allelic: Neuropathy, inflammatory demyelinating (PMP22)
• Allelic: Neuropathy, recurrent, with pressure palsies (PMP22)
• Allelic: Optic atrophy 1 (OPA1)
• Allelic: Osteoarthritis with mild chondrodysplasia (COL2A1)
• Allelic: Osteofibrous dysplasia, susceptibility to (MET)
• Allelic: Otospondylomegaepiphyseal dysplasia, AD + AR (COL11A2)
• Allelic: Pfeiffer syndrome (FGFR2)
• Allelic: Phosphoribosylpyrophosphate synthetase superactivity (PRPS1)
• Allelic: Platyspondylic skeletal dysplasia, Torrance type (COL2A1)
• Allelic: Polyendocrine-polyneuropathy syndrome (DMXL2)
• Allelic: Renal cell carcinoma, papillary, 1, familial + somatic (MET)
• Allelic: Renal hypodysplasia/aplasia 3 (GREB1L)
• Allelic: Retinal disease in Usher syndrome type IIA, modifier of (PDZD7)
• Allelic: Retinitis pigmentosa 39 (USH2A)
• Allelic: Retinitis pigmentosa 61 (CLRN1)
• Allelic: Rhabdomyosarcoma 2, alveolar (PAX3)
• Allelic: Roussy-Levy syndrome (PMP22)
• Allelic: SADDAN [Severe Achondroplasia, Developmental Delay, Acanthosis Nigricans] (FGFR3)
• Allelic: SED congenita (COL2A1)
• Allelic: SMED Strudwick type (COL2A1)
• Allelic: Saethre-Chotzen syndrome (FGFR2)
• Allelic: Scaphocephaly + Axenfeld-Rieger anomaly (FGFR2)
• Allelic: Scaphocephaly with maxillary retrusion + mental retardation (FGFR2)
• Allelic: Short QT syndrome 2 (KCNQ1)
• Allelic: Skin/hair/eye pigmentation 7, blond/brown hair (KITLG)
• Allelic: Spondyloepimetaphyseal dysplasia, XL, with hypomyelinating leukodystrophy (AIFM1)
• Allelic: Spondyloepiphyseal dysplasia, Stanescu type (COL2A1)
• Allelic: Spondyloperipheral dysplasia (COL2A1)
• Allelic: Stickler sydrome, type I, nonsyndromic ocular (COL2A1)
• Allelic: Thanatophoric dysplasia, type I + II (FGFR3)
• Allelic: Very Early Onset Inflammatory Bowel Disease [panelapp] (STXBP3)
• Allelic: Vohwinkel syndrome (GJB2)
• 3-methylglutaconic aciduria with deafness, encephalopathy + Leigh-like syndrome (SERAC1)
• 3MC syndrome 1 (MASP1)
• ABCD syndrome (EDNRB)
• Alport syndrome 1, XL (COL4A5)
• Alstrom syndrome (ALMS1)
• Arts syndrome (PRPS1)
• Auditory neuropathy + optic atrophy (FDXR)
• Auditory neuropathy, AD, 1 (DIAPH3)
• Auditory neuropathy, AR, 1 (OTOF)
• Baraitser-Winter syndrome 2 (ACTG1)
• Bart-Pumphrey syndrome (GJB2)
• Bartter syndrome, type 4a (BSND)
• Bjornstad syndrome (BCS1L)
• Branchiootic syndrome 1 (EYA1)
• Branchiootic syndrome 3 (SIX1)
• Brown-Vialetto-Van Laere syndrome 1 (SLC52A3)
• Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
• CATSHL [CAmptodactyly, Tall Stature, Hearing Loss] syndrome (FGFR3)
• CEBALID syndrome (MN1)
• CHARGE syndrome (CHD7)
• COMMAD syndrome (MITF)
• Cerebellar ataxia, deafness + narcolepsy, AD (DNMT1)
• Charcot-Marie-Tooth disease + deafness (PMP22)
• Charcot-Marie-Tooth disease, type 1E (PMP22)
• Chudley-McCullough syndrome (GPSM2)
• Cochlea malformations [panelapp] (FOXF2)
• Coenzyme Q10 deficiency, primary, 2 (PDSS1)
• Combined oxidative phosphorylation deficiency 24 (NARS2)
• Combined oxidative phosphorylation deficiency 6 (AIFM1)
• Cone-rod dystrophy + hearing loss (CEP78)
• Cone-rod dystrophy and hearing loss 2 (CEP250)
• Congenital disorder of glycosylation, type IIj (COG4)
• Corneal endothelial dystrophy + perceptive deafness (SLC4A11)
• Cowchock syndrome (AIFM1)
• Craniofacial-deafness-hand syndrome (PAX3)
• D-bifunctional protein deficiency (HSD17B4)
• DOORS syndrome (TBC1D24)
• Deafness + myopia (SLITRK6)
• Deafness [panelapp] (SPATC1L)
• Deafness, AD 1, with/-out thrombocytopenia (DIAPH1)
• Deafness, AD 10 (EYA4)
• Deafness, AD 101 (GRXCR2)
• Deafness, AD 11 (MYO7A)
• Deafness, AD 13 (COL11A2)
• Deafness, AD 15 (POU4F3)
• Deafness, AD 17 (MYH9)
• Deafness, AD 20/26 (ACTG1)
• Deafness, AD 22 (MYO6)
• Deafness, AD 22, with hypertrophic cardiomyopathy (MYO6)
• Deafness, AD 23 (SIX1)
• Deafness, AD 25 (SLC17A8)
• Deafness, AD 27 (REST)
• Deafness, AD 28 (GRHL2)
• Deafness, AD 2A (KCNQ4)
• Deafness, AD 2B (GJB3)
• Deafness, AD 34, with/-out inflammation (NLRP3)
• Deafness, AD 36 (TMC1)
• Deafness, AD 37 (COL11A1)
• Deafness, AD 39, with dentinogenesis (DSPP)
• Deafness, AD 3A (GJB2)
• Deafness, AD 3B (GJB6)
• Deafness, AD 40 (CRYM)
• Deafness, AD 41 (P2RX2)
• Deafness, AD 44 (CCDC50)
• Deafness, AD 4A (MYH14)
• Deafness, AD 4B (CEACAM16)
• Deafness, AD 5 (GSDME)
• Deafness, AD 50 (MIR96)
• Deafness, AD 56 (TNC)
• Deafness, AD 6/14/38 (WFS1)
• Deafness, AD 64 (DIABLO)
• Deafness, AD 65 (TBC1D24)
• Deafness, AD 66 (CD164)
• Deafness, AD 67 (OSBPL2)
• Deafness, AD 68 (HOMER2)
• Deafness, AD 69, unilateral or asymmetric (KITLG)
• Deafness, AD 7 (LMX1A)
• Deafness, AD 70 (MCM2)
• Deafness, AD 71 (DMXL2)
• Deafness, AD 72 (SLC44A4)
• Deafness, AD 73 (PTPRQ)
• Deafness, AD 74 (PDE1C)
• Deafness, AD 75 (TRRAP)
• Deafness, AD 76 (PLS1)
• Deafness, AD 77 (ABCC1)
• Deafness, AD 78 (SLC12A2)
• Deafness, AD 79 (SCD5)
• Deafness, AD 8/12 (TECTA)
• Deafness, AD 80 (GREB1L)
• Deafness, AD 81 (ELMOD3)
• Deafness, AD 9 (COCH)
• Deafness, AD [panelapp] (TOP2B)
• Deafness, AD, with peripheral neuropathy (GJB3)
• Deafness, AR (GJB3)
• Deafness, AR 100 (PPIP5K2)
• Deafness, AR 102 (EPS8)
• 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 12 (CDH23)
• Deafness, AR 12, modifier of (ATP2B2)
• Deafness, AR 15 (GIPCY3)
• Deafness, AR 16 (STRC)
• Deafness, AR 18A (USH1C)
• Deafness, AR 18B (OTOG)
• Deafness, AR 1A (GJB2)
• Deafness, AR 1B (GJB6)
• Deafness, AR 2 (MYO7A)
• Deafness, AR 21 (TECTA)
• Deafness, AR 22 (OTOA)
• Deafness, AR 23 (PCDH15)
• Deafness, AR 24 (RDX)
• Deafness, AR 25 (GRXCR1)
• Deafness, AR 26 (GAB1)
• Deafness, AR 28 (TRIOBP)
• Deafness, AR 29 (CLDN14)
• Deafness, AR 3 (MYO15A)
• Deafness, AR 30 (MYO3A)
• Deafness, AR 31 (WHRN)
• Deafness, AR 32, with/-out immotile sperm (CDC14A)
• Deafness, AR 35 (ESRRB)
• Deafness, AR 36 (ESPN)
• Deafness, AR 37 (MYO6)
• Deafness, AR 39 (HGF)
• Deafness, AR 4, with enlarged vestibular aqueduct (SLC26A4)
• Deafness, AR 42 (ILDR1)
• Deafness, AR 44 (ADCY1)
• Deafness, AR 48 (CIB2)
• Deafness, AR 49 (MARVELD2)
• Deafness, AR 53 (COL11A2)
• Deafness, AR 57 (PDZD7)
• Deafness, AR 59 (PJVK)
• Deafness, AR 6 (TMIE)
• Deafness, AR 61 (SLC26A5)
• Deafness, AR 63 (LRTOMT)
• Deafness, AR 66 (DCDC2)
• Deafness, AR 67 (LHFPL5)
• Deafness, AR 68 (S1PR2)
• Deafness, AR 7 (TMC1)
• Deafness, AR 70 (PNPT1)
• Deafness, AR 71 (DFNB71)
• Deafness, AR 74 (MSRB3)
• Deafness, AR 76 (SYNE4)
• Deafness, AR 77 (LOXHD1)
• Deafness, AR 79 (TPRN)
• Deafness, AR 8/10 (TMPRSS3)
• Deafness, AR 84A (PTPRQ)
• Deafness, AR 84B (OTOGL)
• Deafness, AR 86 (TBC1D24)
• Deafness, AR 88 (ELMOD3)
• Deafness, AR 89 (KARS1)
• Deafness, AR 9 (OTOF)
• Deafness, AR 91 (SERPINB6)
• Deafness, AR 93 (CABP2)
• Deafness, AR 94 (NARS2)
• Deafness, AR 97 (MET)
• Deafness, AR 98 (TSPEAR)
• Deafness, AR 99 (TMEM132E)
• Deafness, Dig GJB2/GJB3 (GJB2, GJB3)
• Deafness, Dig GJB2/GJB6 (GJB2, GJB6)
• Deafness, XL 1 (PRPS1)
• Deafness, XL 2 (POU3F4)
• Deafness, XL 4 (SMPX)
• Deafness, XL 5 (AIFM1)
• Deafness, XL 6 (COL4A6)
• Deafness, XL 7 (GPRASP2)
• Deafness, congenital + adult-onset progressive leukoencephalopathy (KARS1)
• Deafness, congenital with inner ear agenesis, microtia + microdontia (FGF3)
• Deafness, congenital, with onychodystrophy, AD (ATP6V1B2)
• Deafness, neurosensory, AR 47 (DFNB47)
• Deafness, neurosensory, without vestibular involvement, AD (ESPN)
• Dejerine-Sottas disease (PMP22)
• Developmental delay, impaired growth, dysmorphic facies, axonal neuropathy (MORC2)
• Diets-Jongmans syndrome (KDM3B)
• Distal renal tubular acidosis 2 with progressive sensorineural hearing loss (ATP6V1B1)
• Duane-radial ray syndrome (SALL4)
• Enlarged vestibular aqueduct (FOXI1)
• Enlarged vestibular aqueduct, Dig (KCNJ10)
• Epilepsy, hearing loss + mental retardation syndrome (SPATA5)
• Epiphyseal dysplasia, multiple, with myopia + deafness (COL2A1)
• Fazio-Londe disease (SLC52A3)
• Fraser syndrome 1: cryptophthalmos, syndactyly, abnormalities of resp. + urogen. tracts (FRAS1)
• Hypoparathyroidism, sensorineural deafness + renal dysplasia (GATA3)
• Hystrix-like ichthyosis with deafness (GJB2)
• IVIC syndrome (SALL4)
• Infantile-onset multisystem neurologic, endocrine + pancreatic disease 2 (YARS)
• Jervell + Lange-Nielsen syndrome (KCNQ1)
• Jervell + Lange-Nielsen syndrome 2 (KCNE1)
• Keratitis-ichthyosis-deafness syndrome (GJB2)
• Keratoderma, palmoplantar, with deafness (GJB2)
• Kilquist syndrome (SLC12A2)
• LADD Lacrimo-auricolo-dento-digitalsyndrome (FGFR2)
• LADD LacrimoAuriculoDentoDigital syndrome (FGF10)
• LADD [LacrimoAuriculoDentoDigital] syndrome (FGFR3)
• Leukoencephalopathy, progressive, infantile-onset, with/-out deafness (KARS1)
• MEDNIK syndrome (AP1S1)
• Macrothrombocytopenia + granulocyte inclusions with/-out nephritis/sensorineural hearing loss (MYH9)
• Mandibulofacial dysostosis with alopecia (EDNRA)
• Mandibulofacial dysostosis, Guion-Almeida type (EFTUD2)
• Marshall syndrome (COL11A1)
• Meier-Gorlin syndrome 4 (CDT1)
• Meier-Gorlin syndrome 5 (CDC6)
• Microphthalmia, syndromic 3 (SOX2)
• Microphthalmia, syndromic 6 (BMP4)
• Microtia with/-out hearing impairment, AD (HOXA2)
• Microtia, hearing impairment + cleft palate, AR (HOXA2)
• Miller syndrome (DHODH)
• Mohr-Tranebjaerg syndrome (TIMM8A)
• Muscular dystrophy, congenital hearing loss + ovarian insufficiency syndrome (GGPS1)
• Nephrotic syndrome, type 14 (SGPL1)
• Neurodevelopmental disorder with hypotonia, neuropathy + deafness (SPTBN4)
• Neuropathy, hereditary sensory, type IE (DNMT1)
• Nonsyndromic genetic deafness [MONDO:0019497] (THOC)
• Optic atrophy plus syndrome (OPA1)
• Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
• Orofacial cleft 11 (BMP4)
• Otofaciocervical syndrome (EYA1)
• PCWH syndrome (SOX10)
• Papillorenal syndrome (PAX2)
• Pendred syndrome (SLC26A4)
• Peripheral neuropathy, myopathy, hoarseness + hearing loss (MYH14)
• Perrault syndrome 1 (HSD17B4)
• Perrault syndrome 2 (HARS2)
• Perrault syndrome 3 (CLPP)
• Perrault syndrome 4 (LARS2)
• Piebaldism (KIT, SNAI2)
• Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa + cataract (ABHD12)
• Profound sensorineural hearing loss [panelapp] (FOXF2)
• Robin sequence with cleft mandible + limb anomalies (EIF4A3)
• SESAME syndrome (KCNJ10)
• Saul-Wilson syndrome (COG4)
• Sensorineural deafness with mild renal dysfunction (BSND)
• Sensorineural hearing impairment [HP:0000407] (RNF220)
• Sensorineural hearing loss (STXBP3)
• Sensorineural hearing loss [panelapp] (TMTC2)
• Stickler syndrome [panelapp] (COL9A3)
• Stickler syndrome, type I (COL2A1)
• Stickler syndrome, type II (COL11A1)
• Stickler syndrome, type IV (COL9A1)
• Stickler syndrome, type V (COL9A2)
• Tietz albinism-deafness syndrome (MITF)
• Townes-Brocks branchiootorenal-like syndrome (SALL1)
• Townes-Brocks syndrome 1 (SALL1)
• Usher syndrome, type 1B (MYO7A)
• Usher syndrome, type 1C (USH1C)
• Usher syndrome, type 1D/F digenic (PCDH15)
• Usher syndrome, type 1G (USH1G)
• Usher syndrome, type 1J (CIB2)
• Usher syndrome, type 2C (ADGRV1)
• Usher syndrome, type 2C, GPR98/PDZD7 digenic (ADGRV1)
• Usher syndrome, type 2C, GPR98/PDZD7 digenic (PDZD7)
• Usher syndrome, type 2D (WHRN)
• Usher syndrome, type 3A (CLRN1)
• Vertebral, cardiac, renal + limb defects syndrome 1 (HAAO)
• Waardenburg syndrome, type 1 (PAX3)
• Waardenburg syndrome, type 2A (MITF)
• Waardenburg syndrome, type 2D (SNAI2)
• Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
• Waardenburg syndrome, type 3 (PAX3)
• Waardenburg syndrome, type 4A (EDNRB)
• Waardenburg syndrome, type 4B (EDN3)
• Waardenburg syndrome, type 4C (SOX10)
• Waardenburg syndrome/ocular albinism, digenic (MITF)
• Wolfram syndrome 1 (WFS1)
• Wolfram syndrome 2 (CISD2)
• Wolfram-like syndrome, AD (WFS1)
• Zimmermann-Laband syndrome 2 (ATP6V1B2)