Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Sep 2003
ReviewCongenital myasthenic syndromes: multiple molecular targets at the neuromuscular junction.
Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis. Defects in ACh resynthesis have now been traced to mutations in choline acetyltransferase. ⋯ The kinetic mutations increase or decrease the synaptic response to ACh and result in slow- and fast-channel syndromes, respectively. Most low-expressor mutations reside in the AChR epsilon subunit and are partially compensated by residual expression of the fetal-type gamma subunit. In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane.
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Ann. N. Y. Acad. Sci. · Sep 2003
ReviewMechanistic diversity underlying fast channel congenital myasthenic syndromes.
A host of missense mutations in muscle nicotinic receptor subunits have been identified as the cause of congenital myasthenic syndromes (CMS). Two classes of CMS phenotypes have been identified: slow channel myasthenic syndromes (SCCMSs) and fast channel myasthenic syndromes (FCCMSs). ⋯ This seemingly rare scenario has arisen with surprisingly high incidence over the past few years, and analyses of the syndromes have revealed a diverse array of mechanisms underlying the pathology. This review focuses on new mechanisms underlying the FCCMS.
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Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis. Several muscle scoring systems have been proposed for assessing muscle strength in such patients. The aim of the present study is to assess the validity and interobserver agreement of these muscle scores.