Autosomal recessive non-syndromic hearing loss

Autosomal recessive nonsyndromic hearing loss presents as sensorineural, conductive or mixed hearing impairment in the absence of visible external-ear abnormalities or additional medical findings involving other organ systems. In most affected individuals, the hearing loss is prelingual and severe to profound, although the spectrum extends from mild to profound, and selected genes (e.g. LOXHD1, TMPRSS3, EPS8L2, BDP1) are associated with progressive postlingual presentations. Approximately 50% of individuals with hearing loss show peripheral vestibular dysfunction on formal evaluation, and approximately 20% of children initially classified as having nonsyndromic hearing loss are subsequently re-classified as syndromic once extra-auditory features emerge.

The estimated congenital prevalence is approximately 1.7 per 1,000 births, rising to an estimated 31 per 1,000 during childhood. Approximately 80% of prelingual hearing loss is attributable to genetic causes, of which approximately 70% is nonsyndromic and approximately 80% follows autosomal recessive inheritance.

The genetic conditions associated with nonsyndromic hearing loss covered on this page predominantly follow autosomal recessive inheritance, as documented in the current overview literature. In approximately 80% of individuals with nonsyndromic genetic hearing loss the condition results from biallelic pathogenic variants and segregates in an autosomal recessive manner. Less common alternative inheritance patterns are described for individual entities.

• Where autosomal recessive nonsyndromic hearing loss is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

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• Van Heurck R, Carminho-Rodrigues MT, Ranza E, Stafuzza C, Quteineh L, Gehrig C, et al. Benefits of exome sequencing in children with suspected isolated hearing loss. Genes (Basel). 2021;12(8):1277. doi:10.3390/genes12081277. PMID:; PMCID: PMC8391342.