title: Long-term follow-up in patients with congenital myasthenic syndrome due to CHAT mutations.
abstract: BACKGROUND
  Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous inherited disorders of the neuromuscular junction. Mutations in the acetylcholine transferase (CHAT) gene cause a pre-synaptic CMS, typically associated with episodic apnoea and worsening of myasthenic symptoms during crises caused by infections, fever or stress. Between crises symptoms may be mild and variable. Acetylcholinesterase - inhibitor therapy is reported to improve clinical symptoms and reduce crises.
  
  
  METHODS
  We present data on the long-term follow-up of 11 patients with a congenital myasthenic syndrome due to nine different CHAT mutations; ten of the patients have not been previously reported.
  
  
  CONCLUSIONS
  Manifestation varied from the neonatal period to the age of two years, follow-up time from nine months to 12 years. This cohort of CHAT patients studied here enabled us to describe two distinct phenotypes: The neonatal-onset group suffers from apnoeic crises, respirator dependency and bulbar weakness. Apnoea should be carefully distinguished from seizures; a CMS should be taken into account early to start appropriate therapy. Infantile-onset patients show mild permanent weakness, but experience apnoeic crises and worsening which resolve with Acetylcholinesterase - inhibitor treatment. However, after several years of treatment proximal muscle strength may decrease and lead to wheelchair dependency despite the continuation of Acetylcholinesterase - inhibitor therapy.
authors.affiliation: Dept. of Paediatric Neurology, University of Essen, Hufelandstr. 55, D-45122 Essen, Germany. ulrike.schara@uk-essen.de
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schara
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Christen
authors.forename: Hacer
authors.initials: H
authors.lastname: Durmus
authors.forename: Marja
authors.initials: M
authors.lastname: Hietala
authors.forename: Kerstin
authors.initials: K
authors.lastname: Krabetz
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rodolico
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schreiber
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voss
authors.forename: Helena
authors.initials: H
authors.lastname: Pihko
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.forename: Juliane S
authors.initials: JS
authors.lastname: Müller
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D001120:Arginine / Q000235:genetics; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics*; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005998:Glycine / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D020294:Myasthenic Syndromes, Congenital / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011950:Receptors, Cholinergic; D006639:Histidine; D001120:Arginine; D002795:Choline O-Acetyltransferase; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D005998:Glycine