Prevalence and Geographical Distribution of Patients With Congenital Myasthenic Syndromes in the United Kingdom

ntroduction/Aims: Congenital myasthenic syndromes (CMS) are often underdiagnosed due to phenotypic overlap with otherneuromuscular disorders. Limited epidemiological data and low awareness hinder early diagnosis, which is key for effectivetreatment. Early recognition of CMS is important as symptomatic treatments often specific for genetic subtypes exist and emerg-ing therapies are in the pipeline. This study aims to estimate the prevalence of genetically confirmed CMS in the United Kingdomand explore geographical variations.Methods: Prevalence was calculated as of 31 December 2023, including genetically confirmed CMS patients residing in theUnited Kingdom and known to be alive. Patients with missing geographic or living status data were excluded. Prevalence wasestimated overall and compared between UK regions served by a highly specialized neuromuscular service (hsNMS) and thosewithout such services (non-hsNMS).Results: A cohort of 442 genetically confirmed CMS patients was identified. CHRNE deficiency, DOK7, RAPSN were the mostcommon subtypes. The UK prevalence was 6.5 cases per million overall and 8.5 cases per million in the pediatric population.The overall prevalence was statistically higher in hsNMS (8.8 cases per million) compared to non-hsNMS regions (5.9 cases permillion). Homozygous patients had a more clustered distribution particularly around urban area.Discussion: Our results suggest there is likely underdiagnosis of CMS in many areas of the United Kingdom and hsNMS mayplay an important diagnostic role. Variations may also be related to other cultural clustering and founder effects. Further re-search should explore how healthcare access, ethnicity, and consanguinity contribute to regional variation and diagnostic rates