The Genetic Causes of Auditory Neuropathy: A Systematic Review

Area of Science:

• Genetics
• Otolaryngology
• Neurology

Background:

• Auditory neuropathy (AN) is a hearing disorder characterized by normal outer hair cell function and abnormal auditory brainstem responses.
• Monogenic factors are significant contributors to the etiology of auditory neuropathy.
• Understanding the genetic basis of AN is crucial for diagnosis and treatment.

Purpose of the Study:

• To systematically review and identify the genetic causes of auditory neuropathy reported in scientific literature.
• To determine the diagnostic yield of genetic testing in individuals diagnosed with auditory neuropathy.

Main Methods:

• A comprehensive systematic search of major biomedical databases (MEDLINE, Embase, PubMed) was performed.
• Studies were included if they reported genetic testing results for individuals with auditory neuropathy, adhering to ACMG criteria for variant interpretation.
• Data from 29 studies involving 441 participants were analyzed.

Main Results:

• Twenty-nine studies identified 21 genes and 136 pathogenic/likely pathogenic variants associated with auditory neuropathy.
• Variants in the OTOF gene were the most frequent genetic cause, accounting for 59% of identified genetic diagnoses.
• Genetic testing yielded a diagnosis in 54% of individuals, with an adjusted diagnostic yield of 31% after accounting for biases.

Conclusions:

• This review consolidates gene and variant associations, advancing the understanding of auditory neuropathy's genetic underpinnings.
• The significant diagnostic yield supports early genetic testing in the auditory neuropathy workup.
• Genetic diagnoses can facilitate precision medicine approaches, including targeted therapies and clinical trial eligibility.