We describe the results of exome sequencing for genetic diagnosis of hearing loss among a clinically heterogeneous cohort of 218 pediatric patients. We found a higher diagnostic rate for unilateral hearing loss than previously reported as well as a significant number of syndromic forms of hearing loss. Based on these results, we advocate for expanded access to genetic testing for phenotypically diverse hearing loss patients.
Objectives
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.
Methods
Trio-based ES was performed for pediatric patients with confirmed HL including those with symmetric, asymmetric, and unilateral HL.
Results
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%).
Conclusion
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.
Level of Evidence
Level IV Laryngoscope, 2022
