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

Abstract

ObjectiveUnilateral 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.

Unilateral Sensorineural Hearing Loss in Children: Etiology, Audiological Characteristics, and Treatment

“…In two out of five children, the etiology of USNHL remained unknown, which is consistent with what has been reported by other studies in the literature [ 29 , 30 ] and makes it difficult to predict the long-term hearing outcomes of these patients. Possible undetected causes of USNHL in the pediatric population might be attributable to genetic variants of unknown/uncertain significance, undiagnosed congenital cytomegalovirus infection (as most cases are asymptomatic at birth), or asymptomatic/paucisymptomatic postnatal infections [ 5 , 10 , 12 ]. This study showed that the characteristics of UNSHL are highly variable regarding age at diagnosis, affected side, degree, hearing changes over time, audiometric configuration, and use of a hearing device.…”

“…The prevalence of UHL increases with age; it is estimated that 7.2% of adults in the United States of America are affected by UHL [ 7 ]. The most common causes of unilateral sensorineural hearing loss (USNHL) include premature birth, congenital or postnatal infections (especially congenital cytomegalovirus and meningitis), structural anomalies (such as cochlear nerve hypoplasia/aplasia and enlarged vestibular aqueduct), genetic underpinnings, and temporal bone trauma [ 6 , 8 , 9 , 10 , 11 , 12 ]; however, in many cases, the etiology remains unknown [ 9 ]. A review by Lieu showed that UHL in children has a negative impact on speech–language development, cognition, and quality of life [ 13 ].…”