The Effects of GJB2 or SLC26A4 Gene Mutations on Neural Response of the Electrically Stimulated Auditory Nerve in Children.

Objectives: This study aimed to (1) investigate the effect of GJB2 and SLC26A4 gene mutations on auditory nerve function in pediatric cochlear implant users and (2) compare their results with those measured in implanted children with idiopathic hearing loss.

Design: Participants included 20 children with biallelic GJB2 mutations, 16 children with biallelic SLC26A4 mutations, and 19 children with idiopathic hearing loss. All subjects except for two in the SLC26A4 group had concurrent Mondini malformation and enlarged vestibular aqueduct. All subjects used Cochlear Nucleus devices in their test ears. For each subject, electrophysiological measures of the electrically evoked compound action potential (eCAP) were recorded using both anodic- and cathodic-leading biphasic pulses. Dependent variables (DVs) of interest included slope of eCAP input/output (I/O) function, the eCAP threshold, and eCAP amplitude measured at the maximum comfortable level (C level) of the anodic-leading stimulus (i.e., the anodic C level). Slopes of eCAP I/O functions were estimated using statistical modeling with a linear regression function. These DVs were measured at three electrode locations across the electrode array. Generalized linear mixed effect models were used to evaluate the effects of study group, stimulus polarity, and electrode location on each DV.

Results: Steeper slopes of eCAP I/O function, lower eCAP thresholds, and larger eCAP amplitude at the anodic C level were measured for the anodic-leading stimulus compared with the cathodic-leading stimulus in all subject groups. Children with GJB2 mutations showed steeper slopes of eCAP I/O function and larger eCAP amplitudes at the anodic C level than children with SLC26A4 mutations and children with idiopathic hearing loss for both the anodic- and cathodic-leading stimuli. In addition, children with GJB2 mutations showed a smaller increase in eCAP amplitude when the stimulus changed from the cathodic-leading pulse to the anodic-leading pulse (i.e., smaller polarity effect) than children with idiopathic hearing loss. There was no statistically significant difference in slope of eCAP I/O function, eCAP amplitude at the anodic C level, or the size of polarity effect on all three DVs between children with SLC26A4 mutations and children with idiopathic hearing loss. These results suggested that better auditory nerve function was associated with GJB2 but not with SLC26A4 mutations when compared with idiopathic hearing loss. In addition, significant effects of electrode location were observed for slope of eCAP I/O function and the eCAP threshold.

Conclusions: GJB2 and SLC26A4 gene mutations did not alter polarity sensitivity of auditory nerve fibers to electrical stimulation. The anodic-leading stimulus was generally more effective in activating auditory nerve fibers than the cathodic-leading stimulus, despite the presence of GJB2 or SLC26A4 mutations. Patients with GJB2 mutations appeared to have better functional status of the auditory nerve than patients with SLC26A4 mutations who had concurrent Mondini malformation and enlarged vestibular aqueduct and patients with idiopathic hearing loss.