Impaired neuromuscular transmission and response to acetylcholinesterase inhibitors in centronuclear myopathies

Neuromuscul Disord. 2011 Jun;21(6):379-86. doi: 10.1016/j.nmd.2011.02.012. Epub 2011 Mar 25.


Many clinical features of autosomal centronuclear myopathies (CNM) and X-linked myotubular myopathy (XLMTM) are common to congenital myasthenic syndromes (CMS). We describe three children whose clinical and electrophysiological findings originally suggested CMS, in whom CNM was diagnosed pathologically, though not yet genetically characterised. A fourth case, with XLMTM, also showed electrophysiological features of a neuromuscular transmission defect. Three (including the XLMTM case) showed improved strength with acetylcholinesterase inhibitor treatment. We also studied neuromuscular junction structure and function in the MTM1 knockdown zebrafish model of XLMTM, demonstrating abnormal neuromuscular junction organization; anticholinesterase therapy resulted in marked clinical response. These observations suggest that a neuromuscular transmission defect may accompany CNM and contribute to muscle weakness. Muscle biopsy should be considered in infants suspected to have CMS, especially if treatment response is incomplete, or no CMS gene mutation is identified. Treatment with acetylcholinesterase inhibitors may benefit some CNM patients. This warrants further confirmation.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Biopsy
  • Child
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterase Inhibitors / therapeutic use*
  • Disease Models, Animal
  • Electromyography
  • Female
  • Gene Knockout Techniques
  • Humans
  • Infant
  • Male
  • Muscle, Skeletal / pathology
  • Myopathies, Structural, Congenital / drug therapy*
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / physiopathology*
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / physiopathology*
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics
  • Pyridostigmine Bromide / pharmacology
  • Pyridostigmine Bromide / therapeutic use
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Treatment Outcome
  • Zebrafish
  • Zebrafish Proteins / genetics


  • Cholinesterase Inhibitors
  • Zebrafish Proteins
  • MTM1 protein, zebrafish
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Pyridostigmine Bromide