Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1)

Objective. This retrospective study describes the phenotype associated with the single most common cause of genetic hearing loss. The frequency of chi ldhood deafness is estimated at 1/500. Half of this hearing loss is genetic and similar to 80% of genetic hearing loss is nonsyndromic and inherited i n an autosomal recessive manner. Approximately 50% of childhood nonsyndromi c recessive hearing loss is caused by mutations in the connexin 26 (Cx26) g ene (GJB2/DFNB1), making it the most common form of autosomal recessive non syndromic hearing loss with a carrier rate estimated to be as high as 2.8%. One mutation, 35delG, accounts for similar to 75% to 80% of mutations at t his gene. Methods. Hearing loss was examined in 46 individuals from 24 families who w ere either homozygous or compound heterozygous for Cx26 mutations. A subset of these individuals were examined for vestibular function, otoacoustic em issions, auditory brainstem response, temporal bone computed tomography, el ectrocardiography, urinalyses, dysmorphology, and thyroid function. Results. Although all persons had hearing impairment, no consistent audiolo gic phenotype was observed. Hearing loss varied from mild-moderate to profo und, even within the group of families homozygous for the common mutation 3 5delG, suggesting that other factors modify the phenotypic effects of mutat ions in Cx26. Furthermore, the hearing loss was observed to be progressive in a number of cases. No associations with inner ear abnormality, thyroid d ysfunction, heart conduction defect, urinalyses, dysmorphic features, or re tinal abnormality were noted. Conclusion. Newborns with confirmed hearing loss should have Cx26 testing. Cx26 testing will help define a group in which similar to 60% will have pro found or severe-profound hearing loss and require aggressive language inter vention (many of these patients will be candidates for cochlear implants).