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

bout 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.