Congenital myasthenic syndrome

Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. The effects of the disease are similar to Lambert-Eaton syndrome and Myasthenia gravis, the difference being that CMS is not an autoimmune disorder.

Symptoms and categories
The types of CMS are classified into three categories: presynaptic, postsynaptic, and synaptic.

Presynaptic symptoms include brief stops in breathing, weakness of the eye, mouth, and throat muscles. These symptoms often result in double vision and difficulty chewing and swallowing. Postsynaptic symptoms in infants include severe muscle weakness, feeding and respiratory problems, and delays in the ability to sit, crawl, and walk. Onset symptoms for all ages may include droopy eyelids. A particular form of postsynaptic CMS (slow-channel CMS) includes severe weakness beginning in infancy or childhood that progresses and leads to loss of mobility and respiratory problems in adolescence or later life. Synaptic symptoms include early childhood feeding and respiratory problems, reduced mobility, curvature of the spine, and weakness, which causes a delay in motor milestones.

Treatment
Treatment depends on the form (category) of the disease. Although symptoms are similar to myasthenia gravis, treatments used in MG are not useful in CMS. MG is treated with immunosuppressants, but the effects of CMS are not caused by the immune system, it is hereditary.

A form of presynaptic CMS is caused by an insufficient release of acetylcholine (ACh) and is treated with cholinesterase inhibitors. Postsynaptic fast-channel CMS (ACh receptors do not stay open long enough) is treated with cholinesterase inhibitors and 3,4-diaminopyridine. Postsynaptic slow-channel CMS is treated with quinidine or fluoxetine, which plugs the ACh receptor. Synaptic CMS has no effective drug treatment.

Low dose treatment with Ephedrine Sulphate has been shown to give some patients temporary improvement in strength. The Ephedrine loses its effectiveness over the course of a few weeks. Once the patient has been off Ephedrine treatment for a few days, the treatment cycle can continue.

Oral doses of the drug Salbutamol (Albuterol)have also shown to be effective in treating symptoms of CMS associated to mutations in Dok-7. Typical dosage is 2 mg, three times per day.