The cause of childhood hearing impairment (excluding infectious pathology of the middle ear) can be extrinsic (embryofoetopathy, meningitis, trauma, drug ototoxicity, noise trauma, etc

Background/Objectives: Waardenburg syndrome (WS) is a genetic disorder characterized by sensorineural hearing loss (SNHL) and pigmentation anomalies. While hearing impairment is a well-established feature of WS, vestibular dysfunction is also reported. This study aimed to investigate vestibular deficits in pediatric WS patients with SNHL, correlating these findings with molecular, audiometric, and radiological data to establish distinct phenotypic profiles for each WS subtype and associated pathogenic variants. Methods: This retrospective study included children with a genetically confirmed diagnosis of WS who underwent vestibular, auditory, and inner ear radiological assessments as part of their routine medical care between July 2000 and May 2022. Data were collected from medical records, including medical history, clinical findings, and assessment results. Results: Vestibular dysfunction was found to be highly prevalent, affecting 64% of the cohort, often impacting the canal sensory organ (89%) and occasionally the otolithic function (33%). Patients with SOX10 pathogenic variations exhibited a markedly higher risk of vestibular dysfunction, highlighting the unique role of SOX10 in inner ear development. Notably, inner ear malformations were identified in all SOX10-mutated subjects, whereas such anomalies were rare among individuals with other WS gene variants, occurring in only two additional cases with minor malformations. Conclusions: This study reveals a significant prevalence of vestibular deficits in pediatric WS patients with SNHL, emphasizing the need for routine vestibular assessments. The higher prevalence and severity of vestibular impairments in SOX10-mutated patients underscore the importance of molecular analysis in clinical diagnosis and management.

Biallelic pathogenic FDXR variations were identified in 2017 as being responsible for sensorial neuropathies. The first reported patients suffered from auditory and optic sensorineural impairments (ANOA, MIM #617717). Since then, many publications have described various phenotypes including peripheral and central nervous systems impairments (MMDS9B, MIM #620887). This is consistent with the role of the encoded protein ferredoxin reductase (FDXR) as one of the actors of iron‐sulfur proteins synthesis in mitochondria. Ophthalmologic and neurologic symptoms have often been reported, but little is known about the associated inner ear disabilities, although hearing loss was described in the early clinical reports. Firstly, we would like to characterize inner ear abnormalities, sharing our observations of five new patients′ hearing and the outcome after rehabilitation. Thereafter, considering the increasing numbers of publications about FDXR , it appeared useful to provide an overview of literature, analyzing how molecular data may correlate with clinical symptoms. We analyzed the clinical and molecular findings in patients reported from 2017 until March 2025. Data included 89 cases from 79 unrelated families. Protein changes were mostly located in the FAD binding domain, whereas those in NADPH binding domains seem to be less prevalent but more related to severe cases with earlier onset symptoms. These data, combined with current knowledge about FDXR catalytic function and its interaction with FDX and/or cytochrome P450 proteins, could help to understand potential phenotype‐genotype correlations.