Slow-Channel Congenital Myasthenic Syndrome Due to the Novel Variant c.1396G_A in CHRNA1 That Responds Favorably to 3,4-Diaminopyridine: A Case Report.

Mutations in are responsible for postsynaptic congenital myasthenic syndromes (CMS) and occur either as slow-channel syndrome or fast-channel syndrome. Slow-channel CMS due to variants responds favorably to pyridostigmine. A patient with slow-channel CMS due to a new variant that responds favorably to 3,4-diaminopyridine (3,4-DAP) has not yet been reported. The patient is a 36-year-old woman who was diagnosed with non-specific CMS at the age of one year when she presented clinically with signs of somnolence, weakness, and facial dysmorphism. She later also developed limb weakness, with the upper limbs being more severely affected. Heat, low humidity, late menstruation, high fever, and stress aggravated the muscle weakness. Only at the age of 17 was pyridostigmine started, which partially improved the muscle weakness. The diagnosis was genetically confirmed when the new, homozygous variant NM_001039523:c.1396G>A in p.(Gly466Arg) was detected at the age of 30. Since then, 3,4-DAP has been administered, which further improved the muscle weakness. In summary, -associated slow-channel CMS may respond favorably not only to pyridostigmine but also to the additional administration of 3,4-DAP. Patients with -associated CMS can live for years without treatment, especially in early life. CMS should be diagnosed without delay to avoid putting people at risk of receiving medication that could potentially worsen their phenotype.