Exome Sequencing Expands the Genetic Diagnostic Spectrum for Pediatric Hearing Loss.

Abstract

Genetic testing is the standard-of-care for diagnostic evaluation of bilateral, symmetric, sensorineural hearing loss (HL). We sought to determine the efficacy of a comprehensive genetic testing method, exome sequencing (ES), in a heterogeneous pediatric patient population with bilateral symmetric, bilateral asymmetric, and unilateral HL. Trio-based ES was performed for pediatric patients with confirmed HL including those with symmetric, asymmetric, and unilateral HL. ES was completed for 218 probands. A genetic cause was identified for 31.2% of probands (n = 68). The diagnostic rate was 40.7% for bilateral HL, 23.1% for asymmetric HL, and 18.3% for unilateral HL, with syndromic diagnoses made in 20.8%, 33.3%, and 54.5% of cases in each group, respectively. Secondary or incidental findings were identified in 10 families (5.52%). ES is an effective method for genetic diagnosis for HL including phenotypically diverse patients and allows the identification of secondary findings, discovery of deafness-causing genes, and the potential for efficient data re-analysis. 4 Laryngoscope, 133:2417-2424, 2023.