Congenital Myasthenic Syndromes (CMS)

Medical Management

The cholinesterase inhibitors used to treat myasthenia gravis (MG) are helpful in some types of congenital myasthenic syndromes (CMS) but may be harmful in others. See below for more.

It’s important to realize that because CMS isn’t an autoimmune disease, it doesn’t respond to immunosuppressant drugs or other treatments aimed at the immune system such as thymectomy.

Cholinesterase inhibitors

These drugs, also known as anticholinesterases, have been used against MG since the early 1990s and can produce relief from symptoms within hours. The one most commonly used is pyridostigmine (Mestinon).

Cholinesterase inhibitors boost levels of acetylcholine (ACh) — a chemical necessary for proper muscle function — not only at the neuromuscular junction but also in the autonomic nervous system (which controls involuntary bodily functions). Sometimes the drugs can cause diarrhea, abdominal cramps, and/or excessive saliva. To minimize these side effects, the physician might lower the dose of cholinesterase inhibitors or prescribe atropine, which blocks the ACh receptors on nerve cells.

The types of CMS that respond to cholinesterase inhibitors include:

• Some forms of presynaptic CMS
• Postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) — In addition to cholinesterase inhibitors, this type is also treated with amifampridine (3,4diaminopyridine) containing drugs that enhance ACh release.

Types of CMS that do not respond to cholinesterase inhibitors include:

• Slow-channel CMS — This type is treated with quinidine or fluoxetine, both of which help to close the ACh receptor channel.
• DOK7-CMS - These patients are treated with albuterol (or salbutamol) or ephedrine.
• Synaptic CMS — These patients are treated with albuterol (or salbutamol) or ephedrine.

Respiratory care

Respiratory care is an important part of CMS management since breathing difficulties can occur in all subtypes of CMS. Some people with CMS may benefit from noninvasive ventilation at home.

Additional reading

• Abicht A, Müller JS, Lochmüller H. Congenital Myasthenic Syndromes Overview. 2003 May 9 [Updated 2021 Dec 23]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1168/
• Ramdas S, Beeson D, Dong YY. Congenital myasthenic syndromes: increasingly complex. Curr Opin Neurol. 2024 Oct 1;37(5):493-501. doi: 10.1097/WCO.0000000000001300. Epub 2024 Jul 25. PMID: 39051439; PMCID: PMC11377046.

Last reviewed: August 2025