Genetic Underpinnings and Audiological Characteristics in Children With Unilateral Sensorineural Hearing Loss

Abstract

AbstractObjectiveUnilateral sensorineural hearing loss (USNHL) is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood USNHL and analyze the associated audiological features.Study DesignRetrospective analysis of a prospectively recruited cohort.SettingTertiary referral center.MethodsWe enrolled 38 children with USNHL between January 1, 2018, and December 31, 2021, and performed physical, audiological, imaging, and congenital cytomegalovirus (cCMV) examinations as well as genetic testing using next‐generation sequencing (NGS) targeting 30 deafness genes. The audiological results were compared across different etiologies.ResultsCausative genetic variants were identified in 8 (21.1%) patients, including 5 with GJB2 variants, 2 with PAX3 variants, and 1 with the EDNRB variant. GJB2 variants were found to be associated with mild‐to‐moderate USNHL in various audiogram configurations, whereas PAX3 and EDNRB variants were associated with profound USNHL in flat audiogram configurations. In addition, whole‐genome sequencing and extended NGS targeting 213 deafness genes were performed in 2 multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and cCMV infection were observed in 9 and 2, respectively, patients without definite genetic diagnoses.ConclusionGenetic underpinnings can contribute to approximately 20% of childhood USNHL, and different genotypes are associated with various audiological features. These findings highlight the utility of genetic examinations in guiding the diagnosis, counseling, and treatment of USNHL in children.