Congenital myasthenic syndromes (CMS) represent a heterogeneous group of disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Clinical, electrophysiologic, and morphologic studies have paved the way for detecting CMS-related mutations in proteins residing in the nerve terminal, the synaptic basal lamina, or in the postsynaptic region of the motor endplate. The disease proteins identified to date include the acetylcholine receptor, acetylcholinesterase, choline acetyltransferase, rapsyn, and Na v1.4, muscle-specific kinase, agrin, β2-laminin, downstream of tyrosine kinase 7, and glutamine-fructose-6- phosphate transaminase 1. Analysis of electrophysiologic and biochemical properties of mutant proteins expressed in heterologous systems have contributed crucially to defining the molecular consequences of the observed mutations and have resulted in improved therapy of most CMS.
- Acetylcholine receptor (AChR)
- Choline acetyltransferase
- Congenital myasthenic syndrome
- Escobar syndrome
- Neuromuscular junction
ASJC Scopus subject areas
- Clinical Neurology