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

Grace Mcmacken,Roger G Whittaker,Hanns Lochmüller,Teresinha Evangelista,Angela Abicht,Marina Dusl

doi:10.1007/s00415-017-8689-3

Abstract

BackgroundCongenital 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.MethodsWe reviewed clinical information from 19 patients with CMS-EA, including patients with mutations in CHAT, SLC5A7 and RAPSN, and patients lacking a genetic diagnosis.ResultsLack 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).ConclusionsA 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.

Highlights

Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a rare but potentially treatable cause of apparent life-threatening events in infancy
The clinical spectrum is increasingly diverse, Congenital myasthenic syndromes (CMS) are characterised by fatigable weakness typically of early onset, a positive family history, and abnormal neurophysiology tests, namely repetitive nerve stimulation (RNS) or single-fibre EMG (SFEMG) [1]
We reviewed the clinical course of 19 patients with CMS-EA, to demonstrate potential diagnostic pitfalls and to assess long-term prognosis

Summary

Introduction

Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a rare but potentially treatable cause of apparent life-threatening events in infancy. 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). 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. Congenital myasthenic syndromes (CMS) are a group of disorders caused by mutations in genes encoding proteins responsible for the function and integrity of the the clinical spectrum is increasingly diverse, CMS are characterised by fatigable weakness typically of early onset, a positive family history, and abnormal neurophysiology tests, namely repetitive nerve stimulation (RNS) or single-fibre EMG (SFEMG) [1]. Increased jitter is more sensitive for detecting impaired neuromuscular transmission than RNS, but is less specific since the findings are essentially identical for both pre- and post-synaptic disorders and must be interpreted along with clinical symptoms and signs

Methods

Results

Conclusion