Journal
EAR AND HEARING
Volume 41, Issue 4, Pages 983-989Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/AUD.0000000000000819
Keywords
Absent cochlear nerves; Cochlear implant outcomes; Cochleovestibular nerve abnormalities; Congenitally absent 8th nerve; Genetics of absent cochlear nerve; Pediatric hearing loss
Funding
- American Hearing Research Foundation
- National Institutes of Health [RO1 DC003594, R01 DC011651, R01 010856]
- Mills Auditory Foundation
Ask authors/readers for more resources
Objective: A small subset of children with congenital hearing loss have abnormal cochleovestibular nerves (i.e., absent, aplastic, or deficient cochlear nerves), with largely unknown etiology. Our objective was to investigate the underlying pathways and identify novel genetic variants responsible for cochleovestibular malformations and nerve abnormalities. It is our hypothesis that several cochleovestibular nerve abnormalities might share common causative pathways. Design: We used a family-based exome sequencing approach to study 12 children with known rare inner ear and/or cochleovestibular nerve malformations. Results: Our results highlight a diverse molecular etiology and suggest that genes important in the developing otic vesicle and cranial neural crest, e.g.,MASP1, GREB1L, SIX1, TAF1, are likely to underlie inner ear and/or cochleovestibular nerve malformations. Conclusions: We show that several cochleovestibular nerve malformations are neurocristopathies, which is consistent with the fact that cochleovestibular nerve development is based on otic placode-derived neurons in close association with neural crest-derived glia cells. In addition, we suggest potential genetic markers for more severely affected phenotypes, which may help prognosticate individual cochlear implantation outcomes. Developing better strategies for identifying which children with abnormal nerves will benefit from a cochlear implantation is crucial, as outcomes are usually far less robust and extremely variable in this population, and current neuroimaging and electrophysiologic parameters cannot accurately predict outcomes. Identification of a suitable treatment early will reduce the use of multiple interventions during the time-sensitive period for language development.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available