Radiologic Phenotyping in Patients with SOX10 Pathogenic Variants: Insights into Neck, Brain, and Temporal Bone Abnormalities
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND PURPOSE: variants are linked to a broad clinical spectrum, including Waardenburg syndrome (WS) in isolation, Kallmann syndrome (KS), as well as an entity characterized by the combination of peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH). This study aims to characterize the full spectrum of abnormalities in the brain, temporal bone, and neck regions, and their syndromic associations. MATERIALS AND METHODS: germline pathogenic variants were included. All underwent MRI, and 9 also had CT of the temporal bone. Imaging and clinical data were systematically analyzed by 2 pediatric neuroradiologists. RESULTS: Phenotypic analysis revealed bilateral temporal bone abnormalities in all patients, mainly characterized by a specific combination of semicircular canal dysplasia/hypoplasia (with high prevalence of severely hypoplastic or absent posterior semicircular canal) and a very reproducible form of cochlear hypoplasia called flattened cochlea. Olfactory bulb agenesis or hypoplasia was identified in all but 2 patients. Other abnormalities include white matter changes suggestive of a hypomyelination pattern or deficient myelination in 4 patients and neck findings typically characterized by parotid gland aplasia/hypoplasia (15/15, 100%) or lacrimal gland aplasia/hypoplasia (13/15, 86%). Clinical phenotypes ranged from sensorineural hearing loss to WS type II or IV and PCWH. CONCLUSIONS: variants and characteristic temporal bone malformations, which, in association with other radiologic abnormalities, represent highly specific diagnostic markers. The constellation of findings reflects the shared neural crest origin of the affected tissues and should always be investigated to support appropriate genetic testing. Early identification of these features via MRI can aid diagnosis, especially in children without classic syndromic signs, and support the patients' management.
DOI: 10.3174/ajnr.a9322
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7140655757