Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSK

Research output: Contribution to journalResearch articleContributedpeer-review


  • Constanze Gallenmüller - , Ludwig Maximilian University of Munich (Author)
  • Wolfgang Müller Felber - , Ludwig Maximilian University of Munich (Author)
  • Marina Dusl - , Ludwig Maximilian University of Munich (Author)
  • Rolf Stucka - , Ludwig Maximilian University of Munich (Author)
  • Velina Guergueltcheva - , Ludwig Maximilian University of Munich, Medical University Sofia (Author)
  • Astrid Blaschek - , Ludwig Maximilian University of Munich (Author)
  • Maja von der Hagen - , Department of Paediatrics, Division of Neuropediatrics (Author)
  • Angela Huebner - , Department of Paediatrics (Author)
  • Juliane S. Müller - , Newcastle University (Author)
  • Hanns Lochmüller - , Newcastle University (Author)
  • Angela Abicht - , Ludwig Maximilian University of Munich, MGZ—Medical Genetics Center (Author)


Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous disorders characterized by a neuromuscular transmission defect. In recent years, causative mutations have been identified in atleast 15 genes encoding proteins of the neuromuscular junction. Mutations in MUSK are known as a very rare genetic cause of CMS and have been described in only three families, world-wide. Consequently, the knowledge about efficient drug therapy is very limited. We identified a novel missense mutation (p.Asp38Glu) heteroallelic to a genomic deletion affecting exons 2-3 of MUSK as cause of a limb-girdle CMS in two brothers of Turkish origin. Clinical symptoms included fatigable limb weakness from early childhood on. Upon diagnosis of a MUSK-related CMS at the age of 16 and 13. years, respectively, treatment with salbutamol was initiated leading to an impressive improvement of clinical symptoms, while treatment with esterase inhibitors did not show any benefit. Our findings highlight the importance of a molecular diagnosis in CMS and demonstrate considerable similarities between patients with MUSK and DOK7-related CMS in terms of clinical phenotype and treatment options.


Original languageEnglish
Pages (from-to)31-35
Number of pages5
JournalNeuromuscular Disorders
Issue number1
Publication statusPublished - Jan 2014

External IDs

researchoutputwizard legacy.publication#54637
Scopus 84891930371
PubMed 24183479



  • Congenital myasthenic syndromes, MUSK-related CMS, Neuromuscular transmission, Salbutamol treatment