Presynaptic Congenital Myasthenic Syndromes
1Department of Neurology, University of California Davis, Sacramento, California, USA.
Muscle & Nerve
|July 1, 2026
Summary
Presynaptic congenital myasthenic syndromes (CMS) impair acetylcholine release, causing muscle weakness and potential autonomic dysfunction. While gene mutations are the cause, treatments focus on managing respiratory issues and symptoms, with gene therapy still in preclinical stages.
Area of Science:
- Neurology
- Genetics
- Molecular Biology
Background:
- Presynaptic congenital myasthenic syndromes (CMS) are rare neuromuscular disorders.
- They result from impaired acetylcholine (ACh) release from motor nerve terminals.
- These conditions manifest as muscle weakness, fatigue, and can involve central and autonomic nervous systems.
Purpose of the Study:
- To review the causes and clinical features of presynaptic CMS.
- To discuss current treatment strategies and their limitations.
- To highlight the potential of future gene therapies.
Main Methods:
- Literature review of presynaptic CMS.
- Analysis of genetic mutations causing CMS.
- Summary of clinical manifestations and treatment outcomes.
Main Results:
- Presynaptic CMS involves either diminished ACh in synaptic vesicles or impaired vesicle release.
- Genetic mutations in ACh synthesis and release proteins are common causes.
- Associated symptoms include muscle weakness, fatigue, apnea, cognitive delay, seizures, and gastrointestinal issues.
Conclusions:
- Effective management of presynaptic CMS involves preventing respiratory complications and symptomatic treatment.
- Pharmacological treatments offer partial relief, and some mild cases improve with age.
- Gene therapy shows promise in preclinical models but is not yet clinically available.
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