Congenital myasthenic syndromes (CMS) are rare and heterogeneous genetic diseases characterized by compromised neuromuscular transmission and clinical features of fatigable weakness; age at onset, presenting symptoms, distribution of weakness, and response to treatment differ depending on the underlying molecular defect. Mutations in one of the multiple genes, encoding proteins expressed at the neuromuscular junction, are currently known to be associated with subtypes of CMS. The most common CMS syndrome identified is associated with mutation in the CHRNE gene, causing principally muscle nicotinic acetylcholine receptor deficiency, that results in reduced receptor density on the postsynaptic membrane.
We describe the clinical, neurophysiological and molecular features of two unrelated CMS Italian families with marked phenotypic variability, carrying the already reported p.T159P mutation in the CHRNE gene. Our report highlights clinical heterogeneity, intrafamily variability in spite of the same genotype and a possible gender effect; it confirms the efficacy and safety of salbutamol in patients who harbor mutations in the epsilon subunit of acetylcholine receptor.