title: A severe congenital myasthenic syndrome with "dropped head" caused by novel MUSK mutations.
abstract: BACKGROUND
  Congenital myasthenic syndromes are rare. Mutations in MUSK were first described in 2004. Thirteen patients have been reported to date, mostly with a relatively mild course. The molecular diagnosis has implications for choice of treatment and genetic counseling.
  
  
  METHODS
  Clinical course and electrophysiological, pathological, and genetic findings were assessed.
  
  
  RESULTS
  We describe the case of a boy with prenatal onset and severe respiratory symptoms with a persisting need for ventilation. The patient had severe bulbar symptoms, marked axial weakness causing a "dropped head," and some facial and proximal weakness. Ophthalmoparesis developed during the first year of life. Salbutamol led to improvement, 3,4-diaminopyridine had a modest effect, but pyridostigmine produced deterioration. Two novel mutations in MUSK were found by whole exome sequencing.
  
  
  CONCLUSIONS
  We expand the phenotype of congenital myasthenic syndromes with MUSK mutations, describing a more severe clinical course with prenatal onset. Predominant bulbar and respiratory weakness with facial and axial weakness and ophthalmoparesis are diagnostic clues.
authors.affiliation: Department of Paediatric Neurology, University Children's Hospital, Steinwiesstrasse 75, 8032, Zürich, Switzerland.
authors.forename: Miriam L
authors.initials: ML
authors.lastname: Giarrana
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Zurich, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Joset
authors.affiliation: Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
authors.affiliation: Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Robb
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Steindl
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Zurich, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Rauch
authors.affiliation: Department of Paediatric Neurology, University Children's Hospital, Steinwiesstrasse 75, 8032, Zürich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Klein
mesh_terms: D002675:Child, Preschool; D006801:Humans; D008297:Male; D018908:Muscle Weakness / Q000209:etiology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020294:Myasthenic Syndromes, Congenital / Q000150:complications / Q000235:genetics*; D009334:Neck Muscles / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D011950:Receptors, Cholinergic / Q000235:genetics*
chemical_list: D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: MUSK; congenital myasthenia; dropped head; ophthalmoparesis; respiratory weakness