Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review

Abstract

Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one dominant allele within the disease gene is sufficient to express the phenotype. Therefore, most patients diagnosed with autosomal dominant non-syndromic HL have a hearing-impaired parent, although de novo mutations should be considered in all cases of negative family history. To date, more than 50 genes and 80 loci have been identified for autosomal dominant non-syndromic HL. DFNA22 (MYO6 gene), DFNA8/12 (TECTA gene), DFNA20/26 (ACTG1 gene), DFNA6/14/38 (WFS1 gene), DFNA15 (POU4F3 gene), DFNA2A (KCNQ4 gene), and DFNA10 (EYA4 gene) are some of the most common forms of autosomal dominant non-syndromic HL. The characteristics of autosomal dominant non-syndromic HL are heterogenous. However, in most cases, HL tends to be bilateral, post-lingual in onset (childhood to early adulthood), high-frequency (sloping audiometric configuration), progressive, and variable in severity (mild to profound degree). DFNA1 (DIAPH1 gene) and DFNA6/14/38 (WFS1 gene) are the most common forms of autosomal dominant non-syndromic HL affecting low frequencies, while DFNA16 (unknown gene) is characterized by fluctuating HL. A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants.

Advanced Omics Techniques for Understanding Cochlear Genome, Epigenome and Transcriptome in Health and Disease

“…Genetic hearing loss that affects any part of the auditory system accounts for ~50% of the deaf population, and can be either non-syndromic (70%) [66,67] or syndromic (30%) [68]. The large heterogeneity of genes engaged in deafness makes it difficult to study and diagnose it [52].…”

Identification of novel MYH14 variants in families with autosomal dominant sensorineural hearing loss

“…While ADNSHL accounts for a smaller proportion of NSHL cases, it can still have a significant impact on affected individuals and their families (Alde et al, 2023;Smith et al, 2005).…”

“…In contrast, autosomal dominant nonsyndromic hearing loss (ADNSHL) typically has post‐lingual onset and is often progressive. While ADNSHL accounts for a smaller proportion of NSHL cases, it can still have a significant impact on affected individuals and their families (Alde et al, 2023; Smith et al, 2005).…”

Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family

“…Among children with genetic abnormalities leading to hearing loss, about 20% exhibit additional findings alongside their hearing impairment ( Gürtler and Lalwani, 2002 ). On the other hand, non-syndromic hearing loss appears as the only issue without affecting other organ systems ( Aldè et al, 2023 ). The causes of both syndromic and non-syndromic hearing loss include genetic mutations and exposure to substances that can harm development ( Cunningham and Tucci, 2017 ; Aldè et al, 2023 ).…”

“…On the other hand, non-syndromic hearing loss appears as the only issue without affecting other organ systems ( Aldè et al, 2023 ). The causes of both syndromic and non-syndromic hearing loss include genetic mutations and exposure to substances that can harm development ( Cunningham and Tucci, 2017 ; Aldè et al, 2023 ).…”