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

J Neurol. 2018 Jan;265(1):194-203. doi: 10.1007/s00415-017-8689-3. Epub 2017 Nov 30.


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 episodes of 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.

Keywords: Congenital myasthenic syndrome; Neuromuscular disease; Neuromuscular junction; Neurophysiology.

MeSH terms

  • Acetylcholinesterase / genetics
  • Adolescent
  • Adult
  • Antibodies / blood
  • Apnea / drug therapy
  • Apnea / genetics*
  • Apnea / physiopathology*
  • Child
  • Child, Preschool
  • Choline O-Acetyltransferase / genetics*
  • Cholinesterase Inhibitors / therapeutic use
  • Collagen / genetics
  • Creatine Kinase / blood
  • Female
  • Humans
  • Infant
  • Longitudinal Studies
  • Male
  • Muscle Proteins / genetics
  • Mutation / genetics*
  • Myasthenia Gravis / drug therapy
  • Myasthenia Gravis / genetics*
  • Myasthenia Gravis / physiopathology*
  • Myosins / genetics
  • Neural Conduction / genetics
  • Receptors, Cholinergic / immunology
  • Receptors, Nicotinic / genetics
  • Respiratory Insufficiency / etiology
  • Retrospective Studies
  • Symporters / genetics


  • Antibodies
  • CHRNE protein, human
  • Cholinesterase Inhibitors
  • MYO9A protein, human
  • Muscle Proteins
  • Receptors, Cholinergic
  • Receptors, Nicotinic
  • SLC5A7 protein, human
  • Symporters
  • peripheral membrane protein 43K
  • Collagen
  • Choline O-Acetyltransferase
  • Creatine Kinase
  • Acetylcholinesterase
  • COLQ protein, human
  • Myosins

Supplementary concepts

  • Congenital myasthenic syndrome with episodic apnea