Non-Syndromic Sensorineural Deafness
Isolated deafness, Isolated hearing loss, Nonsyndromic autosomal dominant deafness, Nonsyndromic autosomal recessive deafness, Nonsyndromic hearing impairment, Nonsyndromic hearing loss and deafness, Nonsyndromic hearing loss
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.
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).