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.Design:
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.Results:
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.Conclusions:
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.