Patterns of neurological manifestations in Woodhouse-Sakati Syndrome

Abstract

BackgroundWoodhouse–Sakati syndrome (WSS) is a rare autosomal recessive disease with characteristic neuro-endocrine manifestations. WSS encompasses heterogeneous phenotypes and disease course. ObjectiveWe aimed to characterize neurological involvement of the disease through subgrouping of core neurological manifestations. MethodsA single-institution retrospective analysis of patients with clinically and genetically confirmed diagnosis of WSS. ResultsA total of 38 individuals belonging to 17 families were identified to have WSS. The mean age at enrollment was 30.1 years (range 16–53 years). Neurological involvement was noted in 31 patients (81.5%). Dystonia was the most common neurological manifestation (67%), followed by intellectual disability (45%) and sensorineural hearing loss (30%). Based on the Neurological Impairment Scale (NIS), the disease was recognized to have two distinct patterns. A disabling, rapidly progressive pattern (NIS of 3–4; Type 1) was noted in eighteen patients (12 males, 6 females; 47.4%) with severe disability that occurs within a mean duration of 7.4 ± 3.6 years. Type 2 WSS was identified in twenty patients (8 males, 12 females; 52.6%), and showed either absent or mild neurological involvement with preserved activities of daily living (NIS of 0–1). The mean age of onset for neurological manifestations was earlier in type 1 (12.6 ± 4.5 years) compared to type 2 (18.1 ± 4.3 years). Type 1 WSS has a significantly higher rate of intellectual disability (p= <0.001). ConclusionsIn this pleiotropic syndrome, we identified two distinct phenotypes with variable prognosis. A high Interfamilial and intrafamilial phenotypic variability despite having a similar gene mutation suggests a possible role of genetic or environmental modifying factor.