Outcome of Cochlear Implantation in Prelingually Deafened Children According to Molecular Genetic Etiology

About 60% of Korean pediatric cochlear implantees could be genetically diagnosed (GD) and we previously reported that a substantial portion of undiagnosed cases by deafness gene panel sequencing were predicted to have a nongenetic or complex etiology. We aimed to compare the outcomes of cochlear implantation (CI) in GD and genetically undiagnosed (GUD) patients and attempted to determine CI outcomes according to etiology.

Ninety-three pediatric cochlear implantees underwent molecular genetic testing. Fifty-seven patients carried pathogenic variants and 36 patients remained GUD after panel sequencing of 204 known or potential deafness genes (TRS-204). Among them, 55 cochlear implantees with reliable speech evaluation results with a follow-up of longer than 24 months were recruited. Longitudinal changes in the audiologic performance were compared between the GD (n = 31) and GUD (n = 24) groups. The GD group was subdivided into cochlear implantee with SLC26A4 mutations (group 1) and cochlear implantee with other genetic etiology (group 2), and the GUD group was subdivided into groups 3 and 4, that is, patients with or without inner ear anomaly, respectively.

Group 1 related to SLC26A4 mutations had the highest categories of auditory perception scores among all groups pre- and postoperatively. Group 4 with inner ear anomaly had the lowest categories of auditory perception scores. At 24 months post-CI, the group 2 with another genetic etiology had significantly better outcomes than molecularly undiagnosed group 3, which had with the same condition as group 2 except that the candidate gene was not detected. This finding was recapitulated when we limited cases to those that underwent CI before 24 months of age to minimize age-related bias at implantation. Furthermore, on extending the follow-up to 36 months postoperatively, this tendency became more prominent. Additionally, our preliminary clinical data suggest a narrower sensitive window period for good CI outcomes for implantees with OTOF mutation rather than the GJB2 and other genes.

Current molecular genetic testing including deafness panel sequencing helps to predict the 2-year follow-up outcomes after CI in prelingually deafened children. GD cochlear implantees show better functional outcomes after CI than undiagnosed cochlear implantees as determined by deafness panel sequencing, suggesting a genotype-functional outcome correlation. The genetic testing may provide a customized optimal window period in terms of CI timing for favorable outcome according to genetic etiology.