Long-Term Cochlear Implant Outcomes in Children with GJB2 and SLC26A4 Mutations

Abstract

ObjectivesTo investigate speech and language outcomes in children with cochlear implants (CIs) who had mutations in common deafness genes and to compare their performances with those without mutations.Study DesignProspective study.MethodsPatients who received CIs before 18 years of age and had used CIs for more than 3 years were enrolled in this study. All patients underwent mutation screening of three common deafness genes: GJB2, SLC26A4 and the mitochondrial 12S rRNA gene. The outcomes with CIs were assessed at post-implant years 3 and 5 using the Categories of Auditory Performance (CAP) scale, Speech Intelligibility Rating (SIR) scale, speech perception tests and language skill tests.ResultsForty-eight patients were found to have confirmative mutations in GJB2 or SLC26A4, and 123 without detected mutations were ascertained for comparison. Among children who received CIs before 3.5 years of age, patients with GJB2 or SLC26A4 mutations showed significantly higher CAP/SIR scores than those without mutations at post-implant year 3 (p = 0.001 for CAP; p = 0.004 for SIR) and year 5 (p = 0.035 for CAP; p = 0.038 for SIR). By contrast, among children who received CIs after age 3.5, no significant differences were noted in post-implant outcomes between patients with and without mutations (all p > 0.05).Conclusion GJB2 and SLC26A4 mutations are associated with good post-implant outcomes. However, their effects on CI outcomes may be modulated by the age at implantation: the association between mutations and CI outcomes is observed in young recipients who received CIs before age 3.5 years but not in older recipients.

Genotype-Phenotype Correlation for Predicting Cochlear Implant Outcome: Current Challenges and Opportunities

“…Moreover, at 3 years after implantation, both homozygous and heterozygous children with mutated SLC26A4 alleles (n = 18 and n = 22 including heterozygotes) demonstrated a better CAP score than children with no detected mutation (n = 75) (Wu et al, 2011). Age is an essential factor in CI performance with this mutation, children older than 3.5 years had no significant differences in post CI performance compared to those without mutations (Wu C.-M. et al, 2015).…”

“…Outer sulcus cells; regulates volume CI before 3.5 years of age, patients show significantly higher CAP/SIR scores than those without mutations 3 years post-implant (Wu C.-M. et al, 2015) At 3 years after implantation, both homozygous and heterozygous children (n = 18 and n = 22 including heterozygotes) had better CAP scores than children with no detected mutation (n = 75) (Wu et al, 2011) Limitations: Effects on CI outcomes may depend on the age of implantation, children older than 3.5 years had no significant differences in post CI performance compared to those without mutations (Wu C.-M. et al, 2015 (Eppsteiner et al, 2012;Usami et al, 2020) Limitations: The causes of the discordant outcomes further investigation.…”

“…This makes patients with SLC26A4 mutations good candidates for CI/EAS. Indeed, studies have shown that post-CI patients have significantly higher CAP/SIR scores than those without mutations 3 years post-implant (Wu C.-M. et al, 2015). Moreover, at 3 years after implantation, both homozygous and heterozygous children with mutated SLC26A4 alleles (n = 18 and n = 22 including heterozygotes) demonstrated a better CAP score than children with no detected mutation (n = 75) (Wu et al, 2011).…”

Auditory synaptopathy, auditory neuropathy, and cochlear implantation

“…Mutations in GJB2 have been shown in multiple studies to be associated with excellent CI outcomes . Similarly, good CI outcomes have been reported in individuals with other genetic lesions affecting the sensory apparatus including mutations in genes that affect the cells of the stria vascularis ( SLC26A4 ), the tip‐links of the stereocilia of the inner hair cells ( CDH23 ), the unconventional myosin motor proteins of the hair cells ( MYO7A ), and the stereocilia structure itself ( LOXHD1 ), among others. One large study of 173 individuals who underwent cochlear implantation showed that any mutation in a deafness‐causing gene affecting the organ of Corti was associated with good CI outcomes .…”

Timing of cochlear implantation in auditory neuropathy patients with OTOF mutations: Our experience with 10 patients

“…Categories of auditory performance (CAP) and speech intelligibility rating (SIR) scores were assessed at 3 months, 6 months, 1 year, 3 years and 5 years post‐implant, whereas speech perception tests were performed at 3 years post‐implant . The duration of CI use in the 10 patients with OTOF mutations ranged from 1 to 7 year as of preparation of this article.…”