Related Experiment Video
Updated: Apr 7, 2026
Systematic Hearing Performance Evaluation Process for Adolescents with Cochlear Implantation at Early Ages
Published on: March 24, 2023
Identifying Children With Poor Cochlear Implantation Outcomes Using Massively Parallel Sequencing
Chen-Chi Wu1, Yin-Hung Lin, Tien-Chen Liu
1From Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan (C-CW, Y-HL, T-CL, K-NL, C-JH); Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan (C-CW, W-SY, P-LC); Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan (Y-HL, P-LC); Department of Otolaryngology, Cardinal Tien Hospital, New Taipei, Taiwan (K-NL); Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan (W-SY, P-LC); Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (W-SY, P-LC); Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan (W-SY, P-LC); Department of Otolaryngology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan (C-JH); and Department of Otolaryngology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan (C-MW).
Insights
Genetic variants in PCDH15 and DFNB59 are linked to poor cochlear implant outcomes in children. Genetic testing before implantation is recommended for all candidates.
Area of Science:
- Genetics
- Otolaryngology
- Pediatrics
Background:
- Cochlear implantation (CI) is a primary treatment for severe to profound hearing loss in children.
- Outcomes following cochlear implantation vary significantly among pediatric recipients.
- Identifying genetic factors influencing CI success is crucial for personalized treatment.
Purpose of the Study:
- To investigate genetic determinants associated with suboptimal outcomes in pediatric cochlear implant recipients.
- To correlate specific genetic variants with audiological, imaging, and performance data in children with poor CI results.
Main Methods:
- Comprehensive genetic analysis using massively parallel sequencing of 129 known deafness genes.
- Comparison of genetic profiles between children with poor CI outcomes (cases) and those with good outcomes (controls).
- Correlation of audiological features, imaging, and CI performance with identified genetic diagnoses.
Main Results:
- Genetic variants linked to poor CI outcomes were found in 58% of cases.
- Bi-allelic PCDH15 mutations and homozygous DFNB59 p.G292R variants were identified in cases.
- Higher allele frequencies of PCDH15 and DFNB59 variants were observed in cases compared to controls (P < 0.001).
- Children with PCDH15 or DFNB59 variants exhibited absent otoacoustic emissions and normal imaging, yet poor CI performance.
Conclusions:
- PCDH15 and DFNB59 variants are significantly associated with poor cochlear implant performance in children.
- Genetic screening for PCDH15 and DFNB59 variants is recommended for all cochlear implant candidates prior to surgery.
- Pre-operative genetic analysis can aid in predicting CI outcomes and guiding treatment strategies.
Abstract:
Cochlear implantation is currently the treatment of choice for children with severe to profound hearing impairment. However, the outcomes with cochlear implants (CIs) vary significantly among recipients. The purpose of the present study is to identify the genetic determinants of poor CI outcomes. Twelve children with poor CI outcomes (the "cases") and 30 "matched controls" with good CI outcomes were subjected to comprehensive genetic analyses using massively parallel sequencing, which targeted 129 known deafness genes. Audiological features, imaging findings, and auditory/speech performance with CIs were then correlated to the genetic diagnoses. We identified genetic variants which are associated with poor CI outcomes in 7 (58%) of the 12 cases; 4 cases had bi-allelic PCDH15 pathogenic mutations and 3 cases were homozygous for the DFNB59 p.G292R variant. Mutations in the WFS1, GJB3, ESRRB, LRTOMT, MYO3A, and POU3F4 genes were detected in 7 (23%) of the 30 matched controls. The allele frequencies of PCDH15 and DFNB59 variants were significantly higher in the cases than in the matched controls (both P < 0.001). In the 7 CI recipients with PCDH15 or DFNB59 variants, otoacoustic emissions were absent in both ears, and imaging findings were normal in all 7 implanted ears. PCDH15 or DFNB59 variants are associated with poor CI performance, yet children with PCDH15 or DFNB59 variants might show clinical features indistinguishable from those of other typical pediatric CI recipients. Accordingly, genetic examination is indicated in all CI candidates before operation.
