OtoSeq Next-Generation DNA Sequencing in the Evaluation of Congenital Sensorineural Hearing Loss

Abstract

Objectives:

Congenital sensorineural hearing loss (SNHL) is relatively common, occurring in 2 to 4 per 1000 infants, with genetic etiologies accounting for nearly 67% of cases. The clinical presentation of patients with syndromic and nonsyndromic SNHL is often indistinguishable. Establishing specific genetic causes is imperative for clinical management and genetic counseling. Recent advances in next-generation sequencing have allowed for facilitated multi-gene testing in genetically heterogeneous conditions such as SNHL. The present study evaluates the clinical utility of one such assay, OtoSeq, in genotyping pediatric patients with SNHL.

Methods:

Demographic, audiometric, imaging, and genetic data were retrospectively collected from 70 patients with prelingual hearing loss who underwent clinical genetic testing of 23 well-studied SNHL genes via OtoSeq, our next generation sequencing platform. The frequencies of pathogenic and likely pathogenic mutations were calculated and audiogram data were reviewed.

Results:

Of 70 patients studied, 15 patients (21%) were found to have an identifiable genetic etiology for their hearing loss, and 8 patients were found to have a previously undiagnosed genetic syndrome. Seven patients were diagnosed with nonsyndromic hearing loss. A total of 27 patients with mutations had adequate audiogram data available, of which 16 had mild to moderate hearing loss (59.3%) and 11 had severe to profound hearing loss (40.7%). Several unique combinations of deafness causing mutations in different genes were identified, including CDH23 and MYO7A, both Usher pathway of genes.

Conclusions:

This study demonstrates that OtoSeq is a valuable tool for determining genetic causes of SNHL in pediatric patients, which has direct implications for their clinical management.