title: [Congenital myasthenic syndromes in childhood: Drug therapeutic strategies].
abstract: Congenital myasthenia syndromes (CMS) are a group of genetic disorders responsible for neuromuscular junction dysfunction. Usually beginning before 2 years of age, they are revealed by fatigability and muscle weakness, especially after stress, and often prevent the child's normal development. Over recent years, major advances in therapeutic strategies have been made following the discovery of numerous mutations responsible for CMS and the understanding of their pathogenic role. Here we report a pediatric CMS case caused by a mutation of the ɛ subunit of the acetylcholine receptor. The initial treatment with acetylcholinesterase inhibitor rapidly showed its limits in terms of both effectiveness and tolerance. The association with 3.4 diaminopyridine (DAP), a new drug available to treat such conditions, has transformed the motor outcome of our patient and allowed psychomotor development. In addition to 3.4 DAP, other molecules adapted to other types of CMS are now available. Three major groups of CMS can be distinguished depending on whether the deficit is at the presynaptic, synaptic, or postsynaptic level of the neuromuscular junction. Depending on the type of CMS, therapeutic management may include acetylcholinesterase inhibitors, 3.4 DAP, fluoxetine, quinidine sulfate, or ephedrine. With the case report, we provide a recent review of the literature on such new therapeutic options, their indications and restrictions, their mechanism of action, and prescription modalities. Knowing the precise CMS type and the appropriate therapeutic options available is essential for the proper management of such chronic and severe but relatively treatable childhood disorders.
authors.affiliation: Unité de neuropédiatrie, hôpital Clocheville, CHRU de Tours, 37044 Tours, France; Service de pédiatrie, hôpital Sud, CHU de Rennes, 35000 Rennes, France.
authors.forename: S
authors.initials: S
authors.lastname: de la Vaissière
authors.affiliation: Unité de génétique, hôpital Clocheville, CHRU de Tours, 37044 Tours, France; Université François-Rabelais de Tours, 37044 Tours, France; UMR Inserm U930, CNRS FRE 2448, 37044 Tours, France.
authors.forename: A
authors.initials: A
authors.lastname: Toutain
authors.affiliation: Unité de médecine pédiatrique, hôpital Clocheville, CHRU de Tours, 37044 Tours, France.
authors.forename: M-A
authors.initials: MA
authors.lastname: Chêne
authors.affiliation: Unité de neuropédiatrie, hôpital Clocheville, CHRU de Tours, 37044 Tours, France; Université François-Rabelais de Tours, 37044 Tours, France; UMR Inserm U930, CNRS FRE 2448, 37044 Tours, France.
authors.forename: E
authors.initials: E
authors.lastname: Lagrue
authors.affiliation: Unité de réanimation pédiatrique, hôpital Clocheville, CHRU de Tours, 37044 Tours, France.
authors.forename: S
authors.initials: S
authors.lastname: Cantagrel
authors.affiliation: Pharmacie, hôpital Clocheville, CHRU de Tours, 37044 Tours, France.
authors.forename: S
authors.initials: S
authors.lastname: Provost
authors.affiliation: Unité de pathologie neuromusculaire, institut de myologie, CHU de la Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Eymard
authors.affiliation: Unité de neuropédiatrie, hôpital Clocheville, CHRU de Tours, 37044 Tours, France; Université François-Rabelais de Tours, 37044 Tours, France; UMR Inserm U930, CNRS FRE 2448, 37044 Tours, France. Electronic address: castelnau@med.univ-tours.fr.
authors.forename: P
authors.initials: P
authors.lastname: Castelnau
mesh_terms: D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D020294:Myasthenic Syndromes, Congenital / Q000188:drug therapy*
chemical_list: D002800:Cholinesterase Inhibitors