Woodhouse-Sakati syndrome presenting with progressive dystonia and white matter disease: a case report and literature review

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive multisystem disorder caused by biallelic pathogenic variants in DCAF17 . It is associated with variable neurological, endocrine, and ectodermal manifestations. This article aims to describe a genetically confirmed case of WSS and to review the neurological and neuroimaging features reported in the literature. We report a 30-year-old Saudi Arabian male with a 13-year history of progressive hoarseness and dysarthria, followed by jaw protrusion, painful oromandibular spasms, impaired chewing, craniocervical and oromandibular dystonia, mild spastic paraparesis, bilateral lower limb dystonia, and a spastic dystonic gait. Brain MRI showed stable periventricular and subcortical white matter lesions without spinal cord involvement. Whole exome sequencing identified a homozygous pathogenic frameshift variant in DCAF17 , c.436del, p.(Ala147Hisfs*9), confirming WSS. The literature review identified 249 individuals from 46 published articles and the present case. Cognitive impairment was the most frequently reported neurological manifestation (63.85%), followed by hearing impairment (46.98%) and movement disorders (46.98%). Dystonia was the predominant movement disorder phenotype, reported in 45.38% of the total reported cohort. Neuroimaging data were available for 197 individuals. Among them, markers of possible iron deposition were the most frequently reported abnormality, present in 40.60% of patients when explicitly reported iron deposition and T2 hypointensity involving deep gray or brainstem structures were considered together. White matter changes were reported in 38.57%, followed by pituitary atrophy or hypoplasia in 35.02%. WSS should be considered in young adults with progressive craniocervical or oromandibular dystonia, dysarthria, endocrine abnormalities, alopecia, characteristic craniofacial features, and white matter lesions. The accompanying literature review reinforces the broad neurological and neuroimaging spectrum of WSS, with dystonia representing the predominant movement disorder phenotype. Recognition of the broader syndromic pattern, supported by molecular confirmation of DCAF17 pathogenic variants, is essential to establish the diagnosis and guide family evaluation.