Childhood Myasthenic Disorders

Abstract

Although the epidemiology of the CMSs is poorly understood, these disorders constitute the major cause of the myasthenic syndrome in the young child and are a minor cause of adult myasthenic syndrome. The diagnosis is often difficult to ascertain because of the frequent absence of a family history of the disease, and because of the pre-eminence of the myopathic signs compared with myasthenic signs. The early onset of the first symptoms, the presence of fluctuations, the demonstration of a neuromuscular block, repetitive CMAP after single stimulation, and the cholinesterase inhibitor test all enable the rectification of the diagnosis and the proposal of an effective treatment and genetic counseling. The numerous studies devoted to CMS over more than 20 years have demonstrated the pathophysiological heterogeneity of CMS. Characterization of the CMS is based on the mode of transmission, the search for a CMAP, the positive or negative response to cholinesterase inhibitors, the study of motor endplates, which is easily done on a deltoid muscle biopsy, and molecular genetics. It will thus be possible to identify the majority of CMSs: a primary anomaly of one of the various acetylcholine receptor subunits, of rapsyn, acetylcholinesterase, ChAT or even SCN4A. However, the origin of a significant fraction of CMSs remains unknown. Numerous molecules of the neuromuscular junction are potential candidates for CMS and may be tested.Therefore, in non-identified cases, various investigations will be used: genetic linkage analysis in the case of large families, the demonstration in the muscle biopsy of a selective deficit in one given synaptic molecule, or microelectrophysiology of the intercostal muscle. Collaboration between clinicians, morphologists, geneticists, and neurobiologists is essential for a complete characterization of the CMSs and for the understanding of the fundamental mechanisms of neuromuscular transmission based on human pathology.

JMG is a rare, autoimmune condition of childhood that shares many characteristics of clinical presentation and management strategies with the adult form of the disease., There are many important aspects that are specific to the paediatric population, in particular the distinct clinical features of the prepubertal presentations, differences in rates of AChR seropositivity, diagnostic challenges including differentiation from CMS, and response to therapy. Further studies looking at efficacy of therapies in pre- and postpubertal children are needed to better understand and support this distinct group of patients