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Congenital myasthenic syndrome due to novel CHAT mutations in an ethnic kadazandusun family
Author(s) -
Tan JooSan,
Ambang Tomica,
AhmadAnnuar Azlina,
Rajahram Giri Shan,
Wong Kum Thong,
Goh Khean Jin
Publication year - 2016
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25037
Subject(s) - congenital myasthenic syndrome , repetitive nerve stimulation , medicine , ptosis , choline acetyltransferase , pyridostigmine , edrophonium , neuromuscular junction , myasthenia gravis , sibling , acetylcholine receptor , endocrinology , acetylcholine , psychology , neuroscience , surgery , developmental psychology , receptor
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. Muscle Nerve 53 : 822–826, 2016