Severe congenital myasthenic syndrome due to homozygosity of the 1293insG epsilon-acetylcholine receptor subunit mutation

Recently, a congenital myasthenic syndrome (CMS) with end-plate acetylcholi ne receptor (AChR) deficiency due to missense mutations in the genes for th e AChR subunit was described. The first observed patient with this CMS was heteroallelic for the two epsilon -AChR subunit mutations epsilon 110insT a nd E1233insG. This patient had only a moderate phenotype with mild muscle w eakness and abnormal fatigue. We have now found homozygosity for the epsilo n 1293insG mutation in a severely affected CMS patient, who lost the abilit y to walk in midchildhood and shows profound weakness and muscle wasting. O ur observation allows a genotype-phenotype correlation illustrating how dif ferences in the AChR mutation haplotype can profoundly influence disease se verity.