Screening Strategies for Deafness Genes and Functional Outcomes in Cochlear Implant Patients

Abstract

Objectives: To review the current state of knowledge about the influence of specific genetic mutations that cause sensorineural hearing loss (SNHL) on cochlear implant (CI) functional outcomes, and how this knowledge may be integrated into clinical practice. A multistep and sequential population-based genetic algorithm suitable for the identification of congenital SNHL mutations before CI placement is also examined.

Data sources, study selection: A review was performed of the English literature from 2000 to 2019 using PubMed regarding the influence of specific mutations on CI outcomes and the use of next-generation sequencing for genetic screening of CI patients.

Conclusion: CI is an effective habilitation option for patients with severe-profound congenital SNHL. However, it is well known that CI outcomes show substantial inter-patient variation. Recent advances in genetic studies have improved our understanding of genotype-phenotype relationships for many of the mutations underlying congenital SNHL, and have explored how these relationships may account for some of the variance seen in CI performance outcomes. A sequential genetic screening strategy utilizing next-generation sequencing-based population-specific gene panels may allow for more efficient mutation identification before CI placement. Understanding the relationships between specific mutations and CI outcomes along with integrating routine comprehensive genetic testing into pre-CI evaluations will allow for more effective patient counseling and open the door for the development of mutation-specific treatment strategies.

FIG. 1.

Population-based genetic workflow for mutational analysis for clinical nonsyndromic SNHL profiling. To detect nonsyndromic SNHL mutations, patients are initially screened for population-specific pathogenic variants in GJB2, GJB6, and mtDNA. If biallelic pathogenic variants are not identified, patients are screened with a global or population-specific gene panel. If a causative mutation cannot be determined, then whole exome sequencing (WES) or whole genome sequencing (WGS) is performed, and if a novel gene is discovered it is added to the appropriate panel for future screening. SNHL indicates sensorineural hearing loss.