Case report: A detour in diagnosis—Waardenburg syndrome

Abstract

Diagnosing rare genetic disorders in children can be particularly challenging, especially when autism spectrum disorder (ASD) is suspected. Waardenburg syndrome (WS) is a rare, genetically heterogeneous condition with a prevalence of approximately 1 in 42,000. It is primarily characterized by congenital hearing loss, pigmented lesions on the skin, eyes, and hair, and distinctive craniofacial features such as telecanthus and a broad nasal bridge. Mutations in genes including PAX3, MITF, EDN3, EDNRB, SOX10, and SNAI2 contribute to its four clinically defined subtypes. We present a child referred for genetic counseling due to suspected ASD, with an initial clinical suspicion of Cornelia de Lange syndrome. Whole exome sequencing, however, identified a pathogenic variant consistent with WS. Although the child lacked classical phenotypic features of WS, the molecular diagnosis prompted reassessment. Notably, intellectual disability in this patient was reconsidered in the context of undiagnosed hearing impairment. As WS accounts for 2–5% of congenital hearing loss, early diagnosis is critical. This case highlights the importance of comprehensive genetic testing in children with neurodevelopmental deviations, as hearing loss associated with WS may mimic or exacerbate features commonly attributed to ASD.