Congenital myasthenic syndromes (CMS) are often underdiagnosed due to phenotypic overlap with other neuromuscular disorders. Limited epidemiological data and low awareness hinder early diagnosis, whic Show more
Congenital myasthenic syndromes (CMS) are often underdiagnosed due to phenotypic overlap with other neuromuscular disorders. Limited epidemiological data and low awareness hinder early diagnosis, which is key for effective treatment. Early recognition of CMS is important as symptomatic treatments often specific for genetic subtypes exist and emerging therapies are in the pipeline. This study aims to estimate the prevalence of genetically confirmed CMS in the United Kingdom and explore geographical variations. Prevalence was calculated as of 31 December 2023, including genetically confirmed CMS patients residing in the United Kingdom and known to be alive. Patients with missing geographic or living status data were excluded. Prevalence was estimated overall and compared between UK regions served by a highly specialized neuromuscular service (hsNMS) and those without such services (non-hsNMS). A cohort of 442 genetically confirmed CMS patients was identified. CHRNE deficiency, DOK7, RAPSN were the most common 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 per million). Homozygous patients had a more clustered distribution particularly around urban area. Our results suggest there is likely underdiagnosis of CMS in many areas of the United Kingdom and hsNMS may play an important diagnostic role. Variations may also be related to other cultural clustering and founder effects. Further research should explore how healthcare access, ethnicity, and consanguinity contribute to regional variation and diagnostic rates. Show less
Congenital Myasthenic Syndromes (CMS) are a group of inherited disorders characterised by fatigable muscle weakness. There are currently no validated outcome measures in CMS. We conducted a prospectiv Show more
Congenital Myasthenic Syndromes (CMS) are a group of inherited disorders characterised by fatigable muscle weakness. There are currently no validated outcome measures in CMS. We conducted a prospective exploratory observational study in 49 CMS patients. The primary aim was to explore relevant and reliable outcome measures for assessing and monitoring change. Assessments included Quantitative Myasthenia Gravis score, Myasthenia Gravis Activities of Daily Living, six-minute-walk-test and sit to stand in one minute, in addition to others. Patients were seen 2-4 times over a 2-year period. Median age was 25.5 (range 1-72) years. Subtypes included AChR-deficiency (n = 15), AGRN-DOK7 clustering complex (n = 15), RAPSN (n = 6), COLQ (n = 5), others (n = 8). Ptosis was highest in AChR-deficiency and limb fatigue was highest in AGRN-DOK7 and COLQ. Median sit to stand in one minute was 22 (range 6-45), median total distance walked in six-minute-walk-test was 434 metres (range 0-711 m). A correlation was noted between sit to stand and six-minute-walk-test (R² = 0.291, p-value <0.001) and between total Quantitative Myasthenia Gravis and Myasthenia Gravis Activities of Daily Living scores (R² = 0.2851, p-value <0.001). This is the first study exploring the use of outcome measures in a CMS population, highlighting the variability in fatigue across CMS subtypes and the limitations of outcome measures validated in myasthenia gravis for CMS. Show less