Background: Waardenburg syndrome (WS) is a hereditary, genetically heterogeneous disorder characterized by variable presentations of sensorineural hearing impairment and pigmentation anomalies. This study aimed to investigate the clinical features of WS in detail and determine the genetic causes of patients with clinically suspected WS.Methods: A total of 24 patients from 21 Han-Taiwanese families were enrolled and underwent comprehensive physical and audiological examinations. We applied targeted next-generation sequencing (NGS) to investigate the potential causative variants in these patients and further validated the candidate variants through Sanger sequencing. Results:We identified 19 causative variants of WS in our cohort. Of these variants, nine were novel and discovered in PAX3, SOX10, EDNRB, and MITF genes, including missense, nonsense, deletion, and splice site variants. Several patients presented with skeletal deformities, hypotonia, megacolon, and neurological disorders that were rarely seen in WS. Conclusion:This study revealed highly phenotypic variability in Taiwanese WS patients and demonstrated that targeted NGS allowed us to clarify the genetic diagnosis and extend the genetic variant spectrum of WS.

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.

Objective: Unilateral sensorineural hearing loss is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood unilateral sensorineural hearing loss and analyze the associated audiological features. Study Design: Retrospective analysis of a prospectively recruited cohort Setting: Tertiary referral center Methods: We enrolled 38 children with unilateral sensorineural hearing loss and performed physical, audiological, imaging, and congenital cytomegalovirus examinations as well as genetic testing using next-generation sequencing targeting 30 deafness genes. The audiological results were compared across different etiologies. Results: Causative genetic variants were identified in eight (21.1%) patients, including five with GJB2 variants, two with PAX3 variants, and one with EDNRB variant. GJB2 variants were associated with mild-to-moderate unilateral sensorineural hearing loss in various audiogram configurations, whereas PAX3 and EDNRB variants were associated with profound unilateral sensorineural hearing loss in flat audiogram configurations. In addition, whole genome sequencing and extended next-generation sequencing targeting 213 deafness genes were performed in two multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and congenital cytomegalovirus infection were observed in nine and two patients without definite genetic diagnoses. Conclusion: Genetic underpinnings can contribute to approximately 20% of childhood unilateral sensorineural hearing loss, 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 unilateral sensorineural hearing loss in children.