Non-Syndromic Sensorineural 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.