Objectives/hypothesis: Our objectives were to determine genotype-phenotype correlations in patients with sensorineural hearing loss (SNHL) who undergo testing for GJB2 mutations and to examine the relationship of temporal bone anomalies seen on computed tomography (CT) and GJB2 mutations.
Study design: We conducted a retrospective review of all children diagnosed with SNHL and who underwent GJB2 testing from 1997 to 2006.
Results: Of 840 patients, 146 (17.4%) had mutations. Seventy-six (9.1%) had biallelic GJB2 mutations and 70 (8.3%) had heterozygous mutations. When biallelic mutations were categorized as missense or nonsense mutations, the presence of at least one missense mutation was associated with mild or moderate SNHL. Biallelic nonsense mutations were associated with severe to profound SNHL. Among patients with GJB2 mutations, those with heterozygous mutations (n = 14 [20%]) had a higher rate of asymmetric SNHL loss than those with biallelic mutations (n = 6 [7.9%], P = .03). Those with heterozygous mutations were more likely to experience progression than were those with biallelic mutations, though this difference was only marginally significant (26.5% vs. 12.3%, respectively; P = .06). Patients who were wild type for GJB2 were more likely to have an enlarged vestibular aqueduct (EVA) than were those with biallelic and heterozygous mutations (29% vs. 11.9%, respectively; P = .004). Compared to patients who were wild type, those with biallelic mutations had a significantly lower rate of EVA.
Conclusions: This is the largest single-institution study of pediatric patients with GJB2 mutations and SNHL. The functional consequences of GJB2 mutations correlated with the degree of hearing loss. Patients with M34T mutations and/or mild SNHL had a low risk of progression. Temporal bone anomalies were uncommon in patients with GJB2 mutations.