What they found
TL;DR (qwen3.6:35b): This systematic review identifies OTOF variants as the primary genetic cause of auditory neuropathy, accounting for 59% of diagnosed cases among 441 participants. The study confirms a diagnostic yield of 54% (adjusted to 31%) for genetic testing, supporting its early use in clinical pathways.
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.
How this applies to our program
While this paper focuses on OTOF rather than STRC/DFNB16, it establishes a critical precedent for the high utility of genetic testing in auditory neuropathy, a condition often overlapping with hair cell dysfunction. This reinforces the importance of comprehensive genetic panels in our program to distinguish between synaptic/neural causes and those involving outer hair cells like STRC.
Key numbers
- 59% of genetic diagnoses were attributed to OTOF variants
- 21 different genes and 136 pathogenic variants were identified across 29 studies
- Diagnostic yield was 54% overall, adjusting to 31% after accounting for study bias
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Connections
[source]auto-indexed 2026-06-13 by strc-lit-watch