Diagnostic Yield in Childhood-Onset Hearing Loss: A Meta-Analysis and Systematic Review

This systematic review and meta-analysis aims to determine the diagnostic yield of whole-exome and targeted-panel sequencing in children with hearing loss. We searched PubMed, Google Scholar, and the Cochrane Library to identify studies describing cohorts of >50 families undergoing whole exome or targeted panel sequencing. Studies were excluded if they pre-screened for common deafness genes without including the data in final analyses, focused on syndromic hearing loss, or lacked diagnostic yield information. Meta-analysis employed a random-effects model of single proportions to determine yield across included studies. The pooled diagnostic yield for bilateral hearing loss was ~47%, while unilateral cases demonstrated a yield of only ~5% across both testing methods. These findings demonstrate that the diagnostic yield for bilateral hearing loss exceeds that of other conditions frequently requiring clinical genetic testing, such as epilepsy and intellectual disability, though this advantage does not extend to unilateral hearing loss. These results have important implications for healthcare policy decisions regarding genetic testing guidelines and funding.