Congenital Myasthenic Syndromes
Congenital myasthenic syndromes (CMS) are disorders of the neuromuscular junction resulting from abnormalities of presynaptic, synaptic, or post synaptic proteins. CMS are characterized by fatigable weakness affecting limb, ocular, facial, and bulbar muscles. Neonates present with feeding problems, choking, feeble cry, and muscle weakness. Patients presenting in later childhood are seen with abnormal exercise-induced fatigue and difficulty running. Most patients present prior to two years of age, although, rare exceptions have been reported (Croxen et al., 2002. PubMed ID:12141216). Symptoms are extremely variable and are in some case induced by febrile illness, infection, or excitement (Byring et al. Neuromuscular Disorders., 2002. PubMed ID:12117478). Life threatening respiratory crises may occur in affected neonates or older children. CMS may be differentiated from myasthenia gravis, an acquired autoimmune disorder, by earlier age of onset and by negative serology tests for anti-acetylcholine receptor (AchR) and anti-Musk antibodies.
A specific diagnosis of CMS is critical as some medications that benefit one type of CMS can be detrimental in another type (Engel, A., 2007. PubMed ID:17395135). When a diagnosed patient is treated with either acetylcholinesterase (AChE) inhibitors or fluoxetine depending on diagnosis, mass improvements in symptoms and a better quality of life is observed (Abicht et al., 2012. PubMed ID: 20301247).
Acetylcholinesterase (AChE) Inhibitor Therapy
Children diagnosed with CMS characterized by post synaptic abnormalities have shown great improvements in neuromuscular capabilities when treated with AChE inhibitors like mestinon (Vajsar et al., 1995. PubMed ID:7619191). Studies done on this therapy, combined with 3,4-diamiopyridine, show it greatly enhances the release of acetylcholine, increases muscles strength by 70-81 percent, nearly doubles the amplitude of compound-muscle-action potential, as well as relieves autonomic symptoms (McEvoy et al., 1989. PubMed ID:8555713).
Fluoxetine therapy performed on patients with Slow Channel CMS (SCCMS) has proven to dramatically improve strength and endurance and allow patients with severe cases to come off of ventilation in less than one month (Colomer et al., 2006. PubMed ID:16621558). This treatment has proven to be effective in long-term management of SCCMS (Harper et al., 2003. PubMed ID:12771277).
For more information on CMS testing, please see our full Test Description
This article is a summary of information that has been reported in the biomedical research literature. It is not medical advice for patients. All disease treatments should be under the direction of a qualified healthcare provider.
Last Updated: 9/18/2017