The Genetic Causes of Auditory Neuropathy: A Systematic Review.
J Clin Med 2026 May 31; 15(11).

Abstract

Background/Objectives:
Auditory neuropathy is a form of hearing loss marked by preserved outer hair cell function and abnormal or absent auditory brainstem responses. Monogenic causes play a significant role in its aetiology. This systematic review aims to identify the genetic causes of auditory neuropathy reported in the literature and to determine the diagnostic yield of genetic testing in affected individuals.
Methods:
A systematic search of MEDLINE, Embase, and PubMed was conducted. Studies were included if participants had a diagnosis of auditory neuropathy and if genetic testing results were reported with variant interpretation based on American College of Medical Genetics and Genomics criteria.
Results/Discussion:
Twenty-nine studies involving 441 children and adults with auditory neuropathy were included. Overall, 21 different genes and 136 pathogenic and likely pathogenic variants were found to be causative of auditory neuropathy, with both syndromic and non-syndromic presentations. Variants in OTOF were the most common cause, responsible for 59% of all genetic diagnoses found. A genetic diagnosis was confirmed in 195 of 362 individuals who underwent genetic testing, resulting in a diagnostic yield of 54%. After adjusting for study bias and new gene associations with AN, the diagnostic yield was 31%.
Conclusions:
This review identifies gene and variant-level associations with auditory neuropathy that enhance our understanding of the condition. It highlights the high diagnostic yield of genetic testing in auditory neuropathy which supports consideration of genetic testing early in the diagnostic pathway. A genetic diagnosis may support precision-based approaches to treatment, including cochlear implants and participation in gene therapy trials.

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Authors+Show Affiliations

Yong N0000-0001-9459-7052Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
Cao MMurdoch Children's Research Institute, Parkville, VIC 3052, Australia. The Royal Children's Hospital, Parkville, VIC 3052, Australia. Victorian Clinical Genetics Services, Parkville, VIC 3052, Australia. Eugene Labs, Richmond, VIC 3121, Australia.
Anderson EMurdoch Children's Research Institute, Parkville, VIC 3052, Australia.
Downie LMurdoch Children's Research Institute, Parkville, VIC 3052, Australia. The Royal Children's Hospital, Parkville, VIC 3052, Australia. Victorian Clinical Genetics Services, Parkville, VIC 3052, Australia. Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Rance GDepartment of Audiology and Speech Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.
Bai J0009-0007-3559-4776Murdoch Children's Research Institute, Parkville, VIC 3052, Australia. Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Liddle K0000-0003-1948-5872Child Health Research Centre, The University of Queensland, South Brisbane, QLD 4101, Australia. Child Development Program, Queensland Children's Hospital, Children's Health Queensland, South Brisbane, QLD 4101, Australia.
Howard AMurdoch Children's Research Institute, Parkville, VIC 3052, Australia. Victorian Clinical Genetics Services, Parkville, VIC 3052, Australia. Eugene Labs, Richmond, VIC 3121, Australia.
Smith L0009-0008-4346-4928Murdoch Children's Research Institute, Parkville, VIC 3052, Australia. The Royal Children's Hospital, Parkville, VIC 3052, Australia.
Sung VMurdoch Children's Research Institute, Parkville, VIC 3052, Australia. The Royal Children's Hospital, Parkville, VIC 3052, Australia. Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Wang J0000-0001-5701-476XMurdoch Children's Research Institute, Parkville, VIC 3052, Australia. Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

42279121