Clinical Report: Molecular and Clinical Spectrum of Epilepsy-Dyskinesia Syndromes

Overview

This multinational cross-sectional study characterized 609 children with childhood-onset movement disorders and pathogenic variants in genes associated with epilepsy-dyskinesia syndromes. Pathogenic variants were found in 74 of 105 predefined genes; clinical features and treatment responses varied by genetic etiology, and epilepsy was reported in approximately two-thirds of patients.

Background

Epilepsy-dyskinesia syndromes are neurogenetic disorders involving overlapping seizure activity and movement disorders. This multinational cross-sectional study used standardized data from more than 30 centers in 25 countries to examine seizure types, movement-disorder phenomenology, development, motor function, and treatment responses in children with childhood-onset movement disorders and pathogenic variants in predefined genes.

Data Highlights

Key Findings

• Dystonia, stereotypies, and ataxia were the most common movement disorders, and most patients had mixed movement-disorder presentations.
• Epilepsy was present in approximately two-thirds of the cohort.
• Pathogenic variants were identified in 74 of 105 predefined genes; 12 genes accounted for two-thirds of cases.
• Unsupervised clustering incorporating protein-protein interaction and functional data identified 12 biologically meaningful gene groups.
• Developmental outcomes and pharmacologic responses varied by genetic etiology and pathway involvement.
• The study reported carbamazepine responsiveness in PRRT2-related disease and worsening motor symptoms with levodopa/carbidopa in patients with GNAO1 and MECP2 variants.

Clinical Implications

The study authors reported variation in developmental outcomes and pharmacologic responses by genetic etiology and pathway involvement. They also reported carbamazepine responsiveness in PRRT2-related disease and worsening motor symptoms with levodopa/carbidopa in patients with GNAO1 and MECP2 variants.

Conclusion

This multinational cross-sectional cohort of 609 children documents genetic and phenotypic diversity among patients with childhood-onset movement disorders and pathogenic variants in genes associated with epilepsy-dyskinesia syndromes. The study identified 12 biologically meaningful gene groups and reported variation in developmental outcomes and pharmacologic responses by genetic etiology and pathway involvement.

Related Resources & Content

1. Quiroz V, et al. Molecular and clinical spectrum of epilepsy-dyskinesia syndromes: a cross-sectional study of 609 patients. Brain. 2026;149(2):563–578. doi:10.1093/brain/awaf297.
2. Epilepsy-Dyskinesia Syndromes: The Venn Diagram of Genetic Epilepsy and Movement Disorders
3. The Broadened Clinical and Genetic Landscape of Disorders Associated with DYNC1H1
4. Clinical and genetic analysis of PRRT2 gene mutations in a cohort of 21 pediatric patients: a case series
5. Epilepsy‐Dyskinesia Syndromes: The Venn Diagram of Genetic Epilepsy and Movement Disorders - Bernardi - Movement Disorders - Wiley Online Library
6. American Epilepsy Society Clinical Practice Guideline: Infantile Epilepsy
7. Outcomes of Bilateral Globus Pallidus Internus Deep Brain Stimulation in GNAO1-Related Disorder: An International Multicenter Experience - PubMed