Congenital myasthenic syndrome due to novel CHAT mutations in an ethnic kadazandusun family

Introduction Choline acetyltransferase (CHAT) gene mutations cause a rare presynaptic congenital myasthenic syndrome due to impaired acetylcholine resynthesis. Methods We report 2 Kadazandusun brothers with novel heterozygous CHAT mutations. Results The siblings were from a family of 7 children of nonconsanguineous parents, 3 who died from apneic crises. Both presented in infancy with ptosis and exertional limb weakness, but only 1 apnea episode was reported in the older sibling. The elder brother had a positive edrophonium test, and both were negative for acetylcholine receptor antibodies but improved with pyridostigmine treatment. A subsequent repetitive nerve stimulation test showed marked decremental response in the abductor digiti minimi only after prolonged ulnar nerve stimulation. Two novel CHAT gene mutations, p.Val306Leu and p.Ser704del were detected; the parents carried 1 mutation each. Conclusions Differences in survival demonstrate phenotypic variability within the same family and a relatively good long-term outcome of the surviving siblings.