Prediction of cochlear implant performance by genetic mutation: The spiral ganglion hypothesis

Abstract

Background Up to 7% of patients with severe-to-profound deafness do not benefit from cochlear implantation. Given the high surgical implantation and clinical management cost of cochlear implantation (> $1 million lifetime cost), prospective identification of the worst performers would reduce unnecessary procedures and healthcare costs. Because cochlear implants bypass the membranous labyrinth but rely on the spiral ganglion for functionality, we hypothesize that cochlear implant (CI) performance is dictated in part by the anatomic location of the cochlear pathology that underlies the hearing loss. As a corollary, we hypothesize that because genetic testing can identify sites of cochlear pathology, it may be useful in predicting CI performance. Methods 29 adult CI recipients with idiopathic adult-onset severe-to-profound hearing loss were studied. DNA samples were subjected to solution-based sequence capture and massively parallel sequencing using the OtoSCOPE® platform. The cohort was divided into three CI performance groups (good, intermediate, poor) and genetic causes of deafness were correlated with audiometric data to determine whether there was a gene-specific impact on CI performance. Results The genetic cause of deafness was determined in 3/29 (10%) individuals. The two poor performers segregated mutations in TMPRSS3, a gene expressed in the spiral ganglion, while the good performer segregated mutations in LOXHD1, a gene expressed in the membranous labyrinth. Comprehensive literature review identified other good performers with mutations in membranous labyrinth-expressed genes; poor performance was associated with spiral ganglion-expressed genes. Conclusions Our data support the underlying hypothesis that mutations in genes preferentially expressed in the spiral ganglion portend poor CI performance while mutations in genes expressed in the membranous labyrinth portend good CI performance. Although the low mutation rate in known deafness genes in this cohort likely relates to the ascertainment characteristics (postlingual hearing loss in adult CI recipients), these data suggest that genetic testing should be implemented as part of the CI evaluation to test this association prospectively.

Massively Parallel Sequencing for Genetic Diagnosis of Hearing Loss

“…The study with the lowest diagnostic rate, Eppsteiner et al 2012, focused on adults with hearing loss and therefore may have had an ascertainment bias towards individuals with environmental or noise-induced non-genetic hearing loss 16 . Gu et al 2014, found a diagnostic rate of 13%, however the patients were strictly pre-screened and were all sporadic patients with no family history of hearing loss 17 .…”

Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

“…The mutations of p.E1957X and c.879+1G>A were novel and p.R1494X had been reported in an American family [13]. LOXHD1 expresses along the plasma membrane of stereocillia.…”

X-Linked Hearing Loss: Two Gene Mutation Examples Provide Generalizable Implications for Clinical Care

“…In DFNX2, the conductive component is atypical; the intracochlear source of the air-bone gap could alter the middle ear and cochlear transfer functions with implications for amplification algorithms, but this has not been investigated in patients with POU3F4 mutations (Petersen et al, 2008;Tang & Parnes, 1994). A more comprehensive understanding of the genotypephenotype correlations associated with different hearing loss etiologies could drive the development of alternative amplification algorithms and also be useful for predicting success with cochlear implantation (Eppsteiner et al, 2012).…”