Congenital myasthenic syndromes.
OBJECTIVE
Congenital myasthenic syndromes are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. In this article, a strategy that leads to the diagnosis of congenital myasthenic syndromes is presented, and recent advances in the clinical, genetic and molecular aspects of congenital myasthenic syndrome are outlined.


RESULTS
Besides the identification of new mutations in genes already known to be implicated in congenital myasthenic syndromes (genes for the acetylcholine receptor subunits and the collagen tail of acetylcholinesterase), mutations in other genes have more recently been discovered and characterized (genes for choline acetyltransferase, rapsyn, and the muscle sodium channel SCN4A). Fluoxetine has recently been proposed as an alternative treatment for 'slow channel' congenital myasthenic syndrome.


CONCLUSIONS
The characterization of congenital myasthenic syndromes comprises two complementary steps: establishing the diagnosis and identifying the pathophysiological type of congenital myasthenic syndrome. Characterization of the type of congenital myasthenic syndrome has allowed it to be classified as caused by presynaptic, synaptic and postsynaptic defects. A clinically and muscle histopathologically oriented genetic study has identified several genes in which mutations cause the disease. Despite comprehensive characterization, the phenotypic expression of one given gene involved is variable, and the aetiology of many congenital myasthenic syndromes remains to be discovered.
Hantaï
Daniel
D
Inserm U582 and Unité Clinique de Pathologie Neuromusculaire, Institut de Myologie, Hôpital de la Salpêtrière, Paris, France. d.hantai@myologie.chups.jussieu.fr
Richard
Pascale
P
Koenig
Jeanine
J
Eymard
Bruno
B
D000110:Acetylcholinesterase / Q000172:deficiency; D000818:Animals; D005838:Genotype; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000502:physiology; D010641:Phenotype; D011379:Prognosis
D009124:Muscle Proteins; C051609:peripheral membrane protein 43K; D000110:Acetylcholinesterase