1. NGS panel - Genetic testing for non-syndromic sensorineural deafness

Non-syndromic sensorineural deafness

April 27, 2018

Disease synonyms

Isolated deafness, Isolated hearing loss, Nonsyndromic autosomal dominant deafness, Nonsyndromic autosomal recessive deafness, Nonsyndromic hearing impairment, Nonsyndromic hearing loss and deafness, Nonsyndromic hearing loss


Disease summary:

Deafness, as inability of an affected person to hear is one of the most common birth defects and it can be caused by a number of different factors, including genetics, environment, birth complications, trauma, certain medications and/or toxins1, 2.

Deafness can be classified as follows2, 3:

  • Conductive deafness that results from abnormalities of the external and/or the middle ear
  • Sensorineural deafness that results from dysfunction of inner ear structures
  • Mixed deafness that is a combination of conductive and sensorineural deafness type
  • Central auditory dysfunction that results from dysfunction of the eighth cranial nerve, auditory brain stem, or cerebral cortex

Hereditary hearing loss can present as syndromic (e.g. associated with abnormalities in other body systems) or non-syndromic (isolated) deafness. It can be inherited in an autosomal dominant or recessive pattern.


Infographics deafness

Autosomal dominant, autosomal recessive

1-3/1,000 newborns worldwide 1, 2

Non-syndromic deafness should be suspected in individuals with the following signs or/and symptoms 2, 3:

  • Congenital non-progressive sensorineural deafness or deficiency that is mild (26-40 dB) to profound (90 dB)
  • Absence of systemic findings identified by clinical/physical examination and medical history
  • Family history of non-syndromic sensorineural deafness.
  • The diagnosis of non-syndromic sensorineural autosomal dominant deafness relies on clinical findings and family history.
  • Diagnosis is confirmed by the identification of pathogenic variant(s) in one of the following genes:
  • Autosomal dominant: ACTG1, CCDC50, COCH, COL11A2, CRYM, DFNA5, DIABLO, DIAPH1, DIAPH3, EYA4, GJB2, GJB3, GJB6, GRHL2, KCNQ4, MIR96, MYH14, MYH9, MYO6, MYO7A, POU3F4, POU4F3, PRPS1, SIX1, SLC17A8, SMPX, TECTA, TJP2, TMC1, WFS1
  • Autosomal recessive: CDH23, CLDN14, COL11A2, DFNB31, DFNB59, ESPN, ESRRB, FOXI1, GIPC3, GJB2, GJB3, GJB6, GPSM2, GRXCR1, HGF, ILDR1, KCNJ10, LHFPL5, LOXHD1, LRTOMT, MARVELD2, MSRB3, MYO15A, MYO3A, MYO6, MYO7A, OTOA, OTOF, PCDH15, POU3F4, PRPS1, PTPRQ, RDX, SERPINB6, SLC12A1, SLC26A4, SLC26A5, SMPX, STRC, TECTA, TMC1, TMIE, TMPRSS3, TPRN, TRIOBP, USH1C

There is no cure for non-syndromic sensorineural deafness to date, but treatment options are available 2.

  • Hearing aids
  • Vibrotactile devices
  • Cochlear implants and many other assisting aids.
  • Otologic surgery.
  • Landau-Kleffner syndrome Usher syndrome type I caused by pathogenic variant in MYO7A, USH1C, CDH23, PCDH15, USH1G, and CIB2
  • Usher syndrome type II caused by pathogenic variant in USH2A, ADGRV1, DFNB31
  • Usher syndrome type III caused by pathogenic variant in CLRN1
  • Pendred syndrome caused by pathogenic variant in SLC26A4
  • Jervell and Lange-Nielsen syndrome caused by pathogenic variant in KCNQ1 or KCNE1

To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for non-syndromic sensorineural autosomal dominant/ autosomal recessive deafness using NGS Panel Genomic:

Step 1: Whole genome sequencing from a single filter card (drop of blood), covering the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the non-syndromic sensorineural autosomal dominant/ autosomal recessive deafness panels. Copy Number Variants analysis derived from NGS data is also included.

Step 2: If no pathogenic variant is identified in Step1, continue with bioinformatics analysis covering genes that are either implicated or associated with overlapping phenotype or similar pathways.  

  • Individuals with a positive family history of non-syndromic sensorineural deafness.
  • Individuals with most common symptoms of non-syndromic sensorineural deafness (regardless of family history).

Confirmation of a clinical diagnosis through genetic testing of non-syndromic sensorineural deafness can allow for genetic counseling and may direct medical management and treatment options.


Genes associated with non-syndromic sensorineural deafness encode structural proteins, cytoskeletal proteins, transcription factors and transmembrane proteins amongst others (Table 1).

Table 1: Overview of genes in Non-syndromic sensorineural autosomal dominant deafness panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ACTG1 102560 Deafness, autosomal dominant 20/26; Baraitser-Winter syndrome 2 AD 8
CCDC50 611051 ?Deafness, autosomal dominant 44 AD 0
COCH 603196 Deafness, autosomal dominant 9 AD 0
COL11A2 120290 Otospondylomegaepiphyseal dysplasia, autosomal dominant; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Deafness, autosomal dominant 13; Deafness, autosomal recessive 53; Fibrochondrogenesis 2 AD, AR 49
CRYM 123740 Deafness, autosomal dominant 40 AD 0
DFNA5 608798 Deafness, autosomal dominant 5 AD 5
DIABLO 605219 Deafness, autosomal dominant 64 AD 1
DIAPH1 602121 Deafness, autosomal dominant 1; Seizures, cortical blindness, microcephaly syndrome AD, AR 4
DIAPH3 614567 Auditory neuropathy, autosomal dominant, 1 AD 2
EYA4 603550 Deafness, autosomal dominant 10; ?Cardiomyopathy, dilated, 1J AD 10
GJB2 121011 Vohwinkel syndrome; Keratitis-ichthyosis-deafness syndrome; Keratoderma, palmoplantar, with deafness; Bart-Pumphrey syndrome; Deafness, autosomal recessive 1A; Deafness, autosomal dominant 3A; Hystrix-like ichthyosis with deafness AD, AR 3
GJB3 603324 Erythrokeratodermia variabilis et progressiva 1; Deafness, digenic, GJB2/GJB3; Deafness, autosomal dominant 2B AD, AR 1
GJB6 604418 Ectodermal dysplasia 2, Clouston type; Deafness, digenic GJB2/GJB6; Deafness, autosomal dominant 3B; Deafness, autosomal recessive 1B AD, AR 8
GRHL2 608576 Deafness, autosomal dominant 28; Ectodermal dysplasia/short stature syndrome AD, AR 2
KCNQ4 603537 Deafness, autosomal dominant 2A AD 4
MIR96 611606 Deafness, autosomal dominant 50 AD 0
MYH14 608568 Deafness, autosomal dominant 4A; ?Peripheral neuropathy, myopathy, hoarseness, and hearing loss AD 19
MYH9 160775 Fechtner syndrome; Epstein syndrome; May-Hegglin anomaly; Macrothrombocytopenia and progressive sensorineural deafness; Deafness, autosomal dominant 17; Sebastian syndrome AD 9
MYO6 600970 Deafness, autosomal dominant 22; Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy; Deafness, autosomal recessive 37 AD, AR 16
MYO7A 276903 Usher syndrome, type 1B; Deafness, autosomal recessive 2; Deafness, autosomal dominant 11 AD, AR 41
POU3F4 300039 Deafness, X-linked 2 XL R 1
POU4F3 602460 Deafness, autosomal dominant 15 AD 3
PRPS1 311850 Gout, PRPS-related; Phosphoribosylpyrophosphate synthetase superactivity; Arts syndrome; Deafness, X-linked 1; Charcot-Marie-Tooth disease, X-linked recessive, 5 XL, XL R 5
SIX1 601205 Deafness, autosomal dominant 23; Branchiootic syndrome 3 AD 0
SLC17A8 607557 Deafness, autosomal dominant 25 AD 3
SMPX 300226 Deafness, X-linked 4 XL D 0
TECTA 602574 Deafness, autosomal dominant 8/12; Deafness, autosomal recessive 21 AD, AR 24
TJP2 607709 Hypercholanemia, familial; Cholestasis, progressive familial intrahepatic 4 AR 9
TMC1 606706 Deafness, autosomal recessive 7; Deafness, autosomal dominant 36 AD, AR 24
WFS1 606201 ?Cataract 41; Diabetes mellitus, noninsulin-dependent, association with; Wolfram syndrome 1; Deafness, autosomal dominant 6/14/38; Wolfram-like syndrome, autosomal dominant AD, AR 16

Abbreviations Table 1: DFNA: Deafness, autosomal dominant; DFNB: Deafness, autosomal recessive; DFNX: Deafness, X-linked; BRWS: Baraitser-Winter syndrome; FBCG: Fibrochondrogenesis; OSMED: Otospondylomegaepiphyseal dysplasia; STL: Stickler syndrome, WZS: Weissenbacher-Zweymuller syndrome; AUNA: Auditory neuropathy, autosomal dominant; CMD: Cardiomyopathy dilated: ECTDS: Ectodermal dysplasia/short stature syndrome; HID: Hystrix-like ichthyosis with deafness; KID: Keratitis-ichthyosis-deafness syndrome; PNMHH: Peripheral neuropathy, myopathy, hoarseness, and hearing loss; EPSTNS: Epstein syndrome; VOWNKL: Vohwinkel syndrome; EKVP: Erythrokeratodermia variabilis with erythema gyratum repens; ECTD: Ectodermal dysplasia Clouston type; USH: Usher syndrome; ARTS: Arts syndrome; MHA: May-Hegglin anomaly; SBS: Sebastian syndrome; CMTX: Charcot-Marie-Tooth disease, X-linked recessive; BOS: Branchiootic syndrome: PFIC: Cholestasis, progressive familial intrahepatic; WFS1: Wolfram syndrome; CTRCT: Cataract.

Table 2: Overview of genes in Non-syndromic sensorineural autosomal recessive deafness panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
CDH23 605516 Usher syndrome, type 1D; Usher syndrome, type 1D/F digenic; Deafness, autosomal recessive 12; Pituitary adenoma 5, multiple types AD, AR, Digenic R 47
CLDN14 605608 Deafness, autosomal recessive 29 AR 2
COL11A2 120290 Otospondylomegaepiphyseal dysplasia, autosomal dominant; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Deafness, autosomal dominant 13; Deafness, autosomal recessive 53; Fibrochondrogenesis 2 AD, AR 49
ESPN 606351 Deafness, autosomal recessive 36 AR 16
ESRRB 602167 Deafness, autosomal recessive 35 AR 11
FOXI1 601093 Enlarged vestibular aqueduct AR 0
GIPC3 608792 Deafness, autosomal recessive 15 AR 8
GJB2 121011 Vohwinkel syndrome; Keratitis-ichthyosis-deafness syndrome; Keratoderma, palmoplantar, with deafness; Bart-Pumphrey syndrome; Deafness, autosomal recessive 1A; Deafness, autosomal dominant 3A; Hystrix-like ichthyosis with deafness AD, AR 3
GJB3 603324 Erythrokeratodermia variabilis et progressiva 1; Deafness, digenic, GJB2/GJB3; Deafness, autosomal dominant 2B AD, AR 1
GJB6 604418 Ectodermal dysplasia 2, Clouston type; Deafness, digenic GJB2/GJB6; Deafness, autosomal dominant 3B; Deafness, autosomal recessive 1B AD, AR 8
GPSM2 609245 Chudley-McCullough syndrome AR 10
GRXCR1 613283 Deafness, autosomal recessive 25 AR 2
HGF 142409 Deafness, autosomal recessive 39 AR 13
ILDR1 609739 Deafness, autosomal recessive 42 AR 6
KCNJ10 602208 Enlarged vestibular aqueduct, digenic; SESAME syndrome AR 3
LHFPL5 609427 Deafness, autosomal recessive 67 AR 2
LOXHD1 613072 Deafness, autosomal recessive 77 AR 14
LRTOMT 612414 Deafness, autosomal recessive 63 AR 7
MARVELD2 610572 Deafness, autosomal recessive 49 AR 2
MSRB3 613719 Deafness, autosomal recessive 74 AR 1
MYO15A 602666 Deafness, autosomal recessive 3 AR 44
MYO3A 606808 Deafness, autosomal recessive 30 AR 38
MYO6 600970 Deafness, autosomal dominant 22; Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy; Deafness, autosomal recessive 37 AD, AR 16
MYO7A 276903 Usher syndrome, type 1B; Deafness, autosomal recessive 2; Deafness, autosomal dominant 11 AD, AR 41
OTOA 607038 Deafness, autosomal recessive 22 AR 31
OTOF 603681 Auditory neuropathy, autosomal recessive, 1; Deafness, autosomal recessive 9 AR 35
PCDH15 605514 Usher syndrome, type 1D/F digenic; Usher syndrome, type 1F; Deafness, autosomal recessive 23 AR, Digenic R 39
PJVK 610219 Deafness, autosomal recessive 59 AR 1
POU3F4 300039 Deafness, X-linked 2 XL R 1
PRPS1 311850 Gout, PRPS-related; Phosphoribosylpyrophosphate synthetase superactivity; Arts syndrome; Deafness, X-linked 1; Charcot-Marie-Tooth disease, X-linked recessive, 5 XL, XL R 5
PTPRQ 603317 Deafness, autosomal recessive 84A; Deafness, autosomal dominant 73 AD, AR 53
RDX 179410 Deafness, autosomal recessive 24 AR 8
SERPINB6 173321 ?Deafness, autosomal recessive 91 AR 12
SLC12A1 600839 Bartter syndrome, type 1 AR 33
SLC26A4 605646 Pendred syndrome; Deafness, autosomal recessive 4, with enlarged vestibular aqueduct AR 12
SLC26A5 604943 ?Deafness, autosomal recessive 61 AR 7
SMPX 300226 Deafness, X-linked 4 XL D 0
STRC 606440 Deafness, autosomal recessive 16 AR 32
TECTA 602574 Deafness, autosomal dominant 8/12; Deafness, autosomal recessive 21 AD, AR 24
TMC1 606706 Deafness, autosomal recessive 7; Deafness, autosomal dominant 36 AD, AR 24
TMIE 607237 Deafness, autosomal recessive 6 AR 3
TMPRSS3 605511 Deafness, autosomal recessive 8/10 AR 9
TPRN 613354 Deafness, autosomal recessive 79 AR 4
TRIOBP 609761 Deafness, autosomal recessive 28 AR 23
USH1C 605242 Usher syndrome, type 1C; Deafness, autosomal recessive 18A AR 25

Abbreviations Table 2: DFNA: Deafness, autosomal dominant; DFNB: Deafness, autosomal recessive; DFNX: Deafness, X-linked; USH: Usher syndrome; BARTS: Bartter syndrome; PDS: Pendred syndrome (Deafness with goiter); DIS: Deafness infertility syndrome; ARNSHL: autosomal recessive nonsyndromic hearing loss; BRWS: Baraitser-Winter syndrome; FBCG: Fibrochondrogenesis;; AUNA: Auditory neuropathy, autosomal dominant; CMCS: Chudley-McCullough syndrome; CMD: Cardiomyopathy dilated: ECTDS: Ectodermal dysplasia/short stature syndrome; HID: Hystrix-like ichthyosis with deafness; KID: Keratitis-ichthyosis-deafness syndrome; PNMHH: Peripheral neuropathy, myopathy, hoarseness, and hearing loss; EPSTNS: Epstein syndrome; VOWNKL: Vohwinkel syndrome; EKVP: Erythrokeratodermia variabilis with erythema; ECTD: Ectodermal dysplasia Clouston type; ARTS: Arts syndrome; MHA: May-Hegglin anomaly; SBS: Sebastian syndrome; CMTX: Charcot-Marie-Tooth disease, X-linked recessive; BOS: Branchiootic syndrome: PFIC: Cholestasis, progressive familial intrahepatic; WFS1: Wolfram syndrome; CTRCT: Cataract.