Clinical and Genetic Features of Congenital Myasthenic Syndromes due to CHAT Mutations: Case Report and Literature Review

Abstract

Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. CMS due to choline acetyltransferase (CHAT) gene is characterized by episodic apnea. We report a case of a 12-month-old female patient presented with recurrent episodic apnea carrying a mutation in CHAT gene, p.I336T. Furthermore, we describe the genetic and clinical findings in 44 CMS patients due to CHAT mutations in the literature up to date. Episodes of apnea and respiratory insufficiency are the hallmarks of CHAT mutations. Clinical manifestations usually provoked by infections and fever. CMS due to CHAT mutations are rare, but it is important to diagnosis. Early diagnosis and appropriate treatment can improve morbidity and mortality.

Congenital Myasthenic Syndrome Due to Compound Heterozygous Mutations in the GFPT1 Gene

“…RNS revealed decrements in abductor digiti minimi and abductor pollicis brevis, and EMG assessment suggested myogenic damage. The proband responded well to an acetylcholinesterase inhibitor, and the phenotypes of the proband were consistent with previous reports of CMS (26)(27)(28). Thus, myasthenia gravis or CMS was initially suspected.…”

AGRN Gene Mutation Leads to Congenital Myasthenia Syndromes: A Pediatric Case Report and Literature Review

“…The congenital myasthenic syndromes (CMS [MIM 608931]) are a group of genetic disorders due to mutations in genes encoding proteins involved in the neuromuscular junction (NMJ) structure and function. 1,2 To date, 32 genes have been reported to be related to CMS, most of which are autosomal recessive, 1 while, some of the slow-channel syndrome genes are transmitted in an autosomal dominant fashion. 3 The AGRN/LRP4/MuSK/Dok-7/Rapsyn pathway is involved in end plate development and maintenance of the NMJ.…”

A Neonate With MuSK Congenital Myasthenic Syndrome Presenting With Refractory Respiratory Failure

“…Although neuroelectrophysiological examination is of great significance for the diagnosis of CMS (15), it is difficult to implement in small infants or newborns owing to its invasive nature. The test with Neostigmine, a cholinesterase inhibitor, is more often used clinically for the diagnosis of myasthenia gravis (18,19) or CMS (17). The positive or negative result of this test is determined through close assessment of the patient's response to Neostigmine before and at every 10 min after the injection.…”

“…A Neostigmine test was carried out on the infant when she was 45 days old. In detail: The Neostigmine was administered at a dose of 0.04 mg•kg-1 by intramuscular injection (15,17). The anterio-posterial chest and abdominal X-ray on DOL23 showed a slightly decreased lung volume with normal lung parenchyma and heart image.…”