Additional clinical manifestations in children with sensorineural hearing loss and biallelic GJB2 mutations: who should be offered GJB2 testing?

Sensorineural hearing loss (SNHL), the most common sensory impairment noted at birth, occurs in 3 out of every 1,000 births live births. At least half of congenital SNHL is genetic in origin, with nonsyndromic, or isolated hearing loss, accounting for approximately 70% of the total genetic causes. Syndromic hearing loss (hearing loss associated with other clinical findings) makes up the remaining 30%. Worldwide, mutations in the gap junction beta 2 (GJB2) gene, encoding the connexin 26 (Cx26) protein, are responsible for approximately 30% of all cases of childhood SNHL. GJB2 mutations have been primarily associated with nonsyndromic forms of bilateral SNHL although rare syndromic forms involving dermatologic manifestations have also been reported. In general, unless skin findings are present, children with bilateral SNHL and other structural or developmental abnormalities are not generally thought of as candidates for GJB2 testing. We evaluated 163 individuals with biallelic GJB2 mutations and SNHL for the presence of other clinical findings. Twenty-nine of the 163 (18%) were found to have structural and/or developmental abnormalities in addition to the SNHL and four subjects had diagnoses that were felt to account for their hearing loss prior to being screened for GJB2 mutations. Although the GJB2 mutations are likely not responsible for these additional clinical manifestations, this study underscores the importance of considering GJB2 mutational analysis in individuals with more than just isolated SNHL given the high prevalence of GJB2-related hearing loss.