A retrospective series of five genetically confirmed Woodhouse-Sakati syndrome patients found bilateral GPi deep brain stimulation produced a mean ~39% improvement in Burke‑Fahn‑Marsden Dystonia Rating Scale scores at 12 months.

Although it offers little mechanistic insight for Parkinson's drug discovery, the study reinforces the clinical efficacy of GPi neuromodulation in severe genetic dystonia and supports the translational relevance of basal ganglia DBS approaches across movement disorders.

BACKGROUND: Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disease with distinctive neuroendocrine manifestations, with dystonia being the most common. No clear guidelines are available for the treatment of dystonia in WSS. OBJECTIVE: The aim was to analyze the impact of deep brain stimulation (DBS) on WSS-associated dystonia. METHODS: Patients with genetically confirmed WSS who underwent globus pallidus internus (GPi) DBS for dystonia were analyzed retrospectively. The participants were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and were videotaped pre- and post-surgery at multiple follow-up points. The primary outcome was the BFMDRS score at 1 year post-surgery, compared with baseline. The primary outcome was correlated with preoperative factors, including age at onset, disease duration at surgery, proportion of life lived with dystonia, and severity rate. RESULTS: Five patients with severe progressive generalized dystonia secondary to clinically and genetically confirmed WSS underwent bilateral GPi DBS from February 2011 through September 2023. The mean age at disease onset and at the time of DBS was 11.3 and 18.6, respectively. All patients' BFMDRS total scores improved from baseline to 12 months post-DBS. The mean pre-DBS BFMDRS score was 71.1, and the mean post-DBS BFMDRS score was 43.6. The percentage improvement in the BFMDRS mean score from pre- to post-DBS was approximately 39%. CONCLUSIONS: Our case series showed clinical improvement in patients who underwent bilateral GPi DBS as an advanced therapy for generalized dystonia secondary to WSS. We recommend further research on DBS in a larger sample of WSS patients to obtain significant results. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.