Causes/Inheritance

What causes congenital myasthenic syndromes (CMS)?

At the normal neuromuscular junction, a nerve cell tells a muscle cell to contract by releasing the chemical acetylcholine (ACh). ACh attaches to the ACh receptor — a pore or "channel" in the surface of the muscle cell — twisting it open and allowing an inward flux of electrical current that triggers muscle contraction. These contractions enable someone to move a hand, dial the telephone, walk through a door or complete any other voluntary movement.

CMS results from flaws in genes necessary for making the ACh receptor or other components of the neuromuscular junction. The many types of CMS are 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).

Presynaptic CMS is caused by insufficient release of ACh; postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) is caused by ACh receptors that are missing or don't stay open long enough; postsynaptic CMS (slow-channel CMS) is caused by ACh receptors that stay open too long; and synaptic CMS is caused by a deficiency of acetylcholinesterase, an enzyme that breaks down ACh.

How is CMS inherited?

With the exception of slow-channel 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 is inherited in an autosomal dominant manner. This means that one copy of a defective ACh receptor gene is enough to cause the disease, so an affected parent has a 50 percent chance of passing the disease on to a child. For more, see Facts about Genetics and Neuromuscular Diseases.