Genotype and Outcomes of Cochlear Implantation in Children With Incomplete Partition Type III.

OBJECTIVES

To investigate the molecular findings and long-term outcomes of cochlear implantation (CI) in a relatively large cohort of patients with incomplete partition type-III malformation (IP-III), and to analyze the correlation between genotype and CI outcomes.

STUDY

DESIGN

Cross-sectional (genomic) and retrospective cohort (auditory and speech outcomes with CI) study.

SETTING

Tertiary referral center.

METHODS

Children diagnosed with IP-III who underwent CI at a tertiary referral center were enrolled. Comprehensive genetic analyses were performed for each participant. Postoperative auditory and speech abilities with CI were retrospectively analyzed. Correlations between different mutation types and CI outcomes were analyzed.

RESULTS

Nineteen children from 17 families were included. All participants had genetic variations, with seven novel variants on the POU3F4 exon and four novel copy number variations (CNVs) on Xq21.1. Most children showed great auditory and speech improvement after long-term rehabilitation with CI, but their speech recognition rates varied considerably. Children with variants affecting amino acid sequences of POU domains showed better preimplantation performance and older age of implantation, but their long-term auditory and speech abilities were comparable to those with complete loss of POU domains. Children with CNVs upstream of POU3F4 had greatly improved auditory and speech abilities, whereas those with large deletions showed only some improvement in sound detection ability.

CONCLUSION

This study expands the mutation spectrum of POU3F4 and provides initial evidence for potential associations between genetic variations and CI outcomes in children with IP-III malformation.

LEVEL OF EVIDENCE: III.