Moritz Thiel, Katerina Bernardi, Enrique Gonzalez Saez‐Diez, Joshua Rong, Nathalie Dorison, Diane Doummar, Claudia Ravelli, Laura A. van de Pol, Joke M. Dijk, Rick Schuurman, Marie Aude Spitz, Christophe Boulloud, Monica Troncoso‐Schifferli, Daniela Munoz‐Chesta, Scellig Stone, Weston T. Northam, Kathryn Yang, Anne Koy, Darius Ebrahimi‐Fakhari
BACKGROUND: ADCY5-related disorder is characterized by disabling hyperkinetic movement disorders. The therapeutic impact of deep brain stimulation (DBS) has not been systematically evaluated. OBJECTIVES/METHODS: This work involved a multicenter cohort study of 8 children with genetically confirmed ADCY5-related movement disorders treated with bilateral globus pallidus internus (GPi) DBS. RESULTS: The mean age at initiation of DBS was 12.9 years (range: 3.5-18). All patients demonstrated improvement in baseline hyperkinesia and paroxysmal exacerbations. Mean Burke-Fahn-Marsden Dystonia Rating Scale motor scores decreased from 50.7 to 22.7 (p = 0.019, d = 1.19). Functional gains included new or recovered motor milestones, improved speech and swallowing, and resolution of sleep-related dyskinesias. There were no perioperative complications. CONCLUSIONS: GPi-DBS is a safe and effective therapy for ADCY5-related movement disorders, offering sustained motor and functional improvement. These findings support earlier consideration of DBS to reduce disease burden, preserve function, and improve long-term outcomes. © 2026 International Parkinson and Movement Disorder Society.