Clinical variability of CMS-EA (congenital myasthenic syndrome with episodic apnea) due to identical CHAT mutations in two infants

Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction

“…We determined the complete genomic structure of CHAT encoding ChAT, and identified ten mutations in five CMS patients with the characteristic clinical features of sudden episodes of apnea associated with variable myasthenic symptoms (Ohno et al, 2001). Additional CHAT mutations were later reported by other groups Schmidt et al, 2003;Barisic et al, 2005;Mallory et al, 2009;Yeung et al, 2009;Schara et al, 2010). All of our patients showed a marked decrease of the endplate potential after subtetanic stimulation that recovered slowly over 5 to 10 min, which pointed to a defect in the resynthesis or vesicular packaging of ACh at the nerve terminal.…”

Congenital myasthenic syndromes: spotlight on genetic defects of neuromuscular transmission

“…87), which may indicate a founder effect in the Turkish population. The compound heterozygous combination of the mutations L210P with S498L and S694C with T354M have each been found in two independent patients from Finland and Croatia, respectively (Refs 11,88).…”

Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes

“…6 The course of disease seems to follow two distinct trends with either neonatal onset respiratory distress with progressive improvement over time but then further respiratory relapses in adulthood or late onset (during infancy or childhood) respiratory crises with a more unpredictable course of disease. [25][26] Treatment is with AChE inhibitor therapy in variable doses with or without addition of 3, 4-diaminopyridine (3, 4 DAP) 27 . There is some recent anecdotal evidence that midazolam may mitigate the severity of apnoeic episodes but further study is needed.…”