Shillito_1993_Neuromuscul.Disord_3_183

The Congenital Myasthenic Syndromes (CMS) constitute a group of rare genetic disorders affecting neuromuscular transmission. They differ from myasthenia gravis and the Lambert-Eaton myasthenic syndrome, which are autoimmune antibody-mediated conditions. CMS can present at any time from birth to adulthood, though usually within the first 2 yr of life, and result in a spectrum of diseases ranging from mild weakness to severe disability with life-threatening episodes. Several of these syndromes have been well documented, and in recent years fully investigated using a variety of electrophysiological, histochemical, and morphological techniques. In this review we describe the main results of these investigations, and attempt to classify the disorders into groups that can be recognized by the clinician. They include defects in acetylcholine release, absence of the endplate-specific form of acetylcholinesterase, and alterations in the number or function of postsynaptic acetylcholine receptors. Clinical features are described in detail, and treatment reviewed. These disorders involve a potentially large number of candidate genes. Further elucidation of the underlying abnormalities will not only lead to improved treatment, but should contribute to our understanding of the molecular biology of the neuromuscular junction.