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Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological and genetic features in the long-term follow-up of 19 patients

Lookup NU author(s): Dr Grace McMacken, Professor Roger Whittaker, Dr Teresinha Evangelista, Professor Hanns Lochmuller



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2017 The Author(s) Background: Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a rare but potentially treatable cause of apparent life-threatening events in infancy. The underlying mechanisms for sudden and recurrent episodesof respiratory arrest in these patients are unclear. Whilst CMS-EA is most commonly caused by mutations in CHAT, the list of associated genotypes is expanding. Methods: We reviewed clinical information from 19 patients with CMS-EA, including patients with mutations in CHAT, SLC5A7 and RAPSN, and patients lacking a genetic diagnosis. Results: Lack of genetic diagnosis was more common in CMS-EA than in CMS without EA (56% n = 18, compared to 7% n = 97). Most patients manifested intermittent apnoea in the first 4 months of life (74%, n = 14). A degree of clinical improvement with medication was observed in most patients (74%, n = 14), but the majority of cases also showed a tendency towards complete remission of apnoeic events with age (mean age of resolution 2 years 5 months). Signs of impaired neuromuscular transmission were detected on neurophysiology studies in 79% (n = 15) of cases, but in six cases, this was only apparent following specific neurophysiological testing protocols (prolonged high-frequency stimulation). Conclusions: A relatively large proportion of CMS-EA remains genetically undiagnosed, which suggests the existence of novel causative CMS genes which remain uncharacterised. In light of the potential for recurrent life-threatening apnoeas in early life and the positive response to therapy, early diagnostic consideration of CMS-EA is critical, but without specific neurophysiology tests, it may go overlooked.

Publication metadata

Author(s): McMacken G, Whittaker RG, Evangelista T, Abicht A, Dusl M, Lochmuller H

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2018

Volume: 265

Issue: 1

Pages: 194-203

Print publication date: 01/01/2018

Online publication date: 30/11/2017

Acceptance date: 20/11/2017

Date deposited: 14/12/2017

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Springer Berlin Heidelberg


DOI: 10.1007/s00415-017-8689-3


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