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
Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes, a rare heterogeneous group of neuromuscular disorders caused by genetic defects impa Show more
Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes, a rare heterogeneous group of neuromuscular disorders caused by genetic defects impacting the structure and function of the neuromuscular junction. Recurrent, life-threatening episodic apnoea in early infancy and childhood and progressive respiratory failure requiring ventilation are features of certain genotypes of congenital myasthenic syndromes. Robb Show less