Congenital Myasthenic Syndromes: A Retrospective Natural History Study of Respiratory Outcomes in A Single Centre

Abstract Respiratory problems are a major cause of morbidity and mortality in patients with congenital myasthenic syndromes (CMS), 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, as well as progressive respiratory failure requiring ventilation are features of certain genotypes of CMS. Robb et al published empirical guidance on respiratory management of the congenital myasthenic syndromes, but other than this workshop report, there is little published longitudinal natural history data on respiratory outcomes of these disorders. We report a retrospective, single-centre study on respiratory outcomes in a cohort of 40 well characterised genetically confirmed cases of CMS, including 10 distinct subtypes (DOK7, COLQ, RAPSN, CHAT, CHRNA1, CHRNG, COL13A1, CHRNE, CHRNE fast channel syndrome and CHRNA1 slow channel syndrome), with many followed up over 20 years in our centre. A quantitative and longitudinal analysis of key spirometry and sleep study parameters, as well as a description of historical hospital admissions for respiratory decompensation, provides a snapshot of the respiratory trajectory of CMS patients based on genotype.