The Genetic Causes of Auditory Neuropathy: A Systematic Review

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.