Congenital Myasthenic Syndromes (CMS)

Congenital Myasthenic Syndromes (CMS)

What are congenital myasthenic syndromes (CMS)?

Like myasthenia gravis (MG), CMS is characterized by weakness and fatigue resulting from problems at the neuromuscular junction— the place where nerve and muscle cells meet (see illustration at right). But while MG is autoimmune, CMS is an inherited disease caused by defective genes.

There are many types of CMS, grouped into three main categories named for the part of the neuromuscular junction that’s affected: presynaptic (the nerve cell), postsynaptic (the muscle cell) or synaptic (the space in between).

What are the symptoms of CMS?

Depending on the type, symptoms of CMS vary from mild to severe, but generally include weakness, fatigue and ptosis (droopy eyelids). However, ptosis may not be present in some forms. The earlier the onset of CMS, the more severe the symptoms are likely to be.

What causes CMS?

With the exception of slow-channel CMS and some presynaptic CMS, the inheritance pattern for the types of CMS described here is autosomal recessive. This means that it takes two copies of the defective gene — one from each parent — to cause the disease.

Slow-channel CMS and some presynaptic CMS is inherited in an autosomal dominant manner. This means that one copy of a defective gene is enough to cause the disease, so an affected parent has a 50% chance of passing the disease on to a child.

For more, see Causes/Inheritance.

What is the progression of CMS?

As its name implies, CMS usually has a congenital (at or near birth) onset, but it can manifest in children and even in adults. Later-onset cases tend to be milder.

What is the status of research on CMS?

By identifying the genetic defects that cause CMS, scientists have improved the diagnosis of CMS and discovered drugs that are effective against it. They’re pursuing better drug treatments, and eyeing techniques to fix or replace the underlying genetic defects by gene therapy. For more, see Research.

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/
• Ohno K, Ohkawara B, Shen XM, Selcen D, Engel AG. Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review. Int J Mol Sci. 2023;24:3730.

Last reviewed: August 2025