Unravelling the Global Tapestry of Genetic Ataxias: Epidemiology and Genetic Testing Approaches

Abstract

The landscape of genetic ataxias is influenced by migration, population genetics, consanguinity, and founder effects, resulting in significant regional variation. Within the expanding domain of genetic ataxias, knowledge of regional epidemiology is scarce, particularly outside of North America and Europe. Understanding the epidemiology of genetic ataxias, together with deep phenotyping and knowledge of the appropriate ancillary studies, is crucial for the development and deployment of diagnostic testing strategies. This review offers a comprehensive, data-driven overview of 2932 articles with regional epidemiological estimates and the occurrence and prevalence of 548 genes associated with ataxia across 122 countries. Regional differences in epidemiology and phenotypic spectra are highlighted, driving an approach that incorporates complementary diagnostic test results and how these may inform cost-effective, region-specific genetic testing. All data are also publicly available as an online database, the MDSGene Global Genetic Ataxia Resource, accessible at https://www.mdsgene.org/ataxia.html. A phenotype-guided, tailored, and sequential testing approach is proposed, based on regional prevalence, to assist clinicians worldwide in diagnosing individuals with presumed genetic ataxia, of which at least 45 causes are treatable. This approach is particularly important in underserved regions, but also in developed countries where health systems limit access to genetic testing, improving the cost-effectiveness and feasibility of genetic testing in these areas. Future screening studies in high-income settings should adopt a more comprehensive approach, integrating broader genetic testing that covers the full range of genetic ataxias. Capacity building for genetic screening in underserved regions, particularly in Africa, South America, and the Middle East, should be prioritized. © 2025 International Parkinson and Movement Disorder Society.