A congenital myasthenic syndrome refractory to acetylcholinesterase inhibitors

Muscle Nerve. 1992 Mar;15(3):267-72. doi: 10.1002/mus.880150302.


We studied 4 siblings (3 men and 1 woman), ages 22 to 43 years, with congenital ptosis, external ophthalmoplegia, proximal muscle weakness and fatigability unresponsive to acetylcholinesterase (AChE) inhibitors. Repetitive nerve stimulation showed a significant compound muscle action potential (CMAP) area decrement at 2 or 3 Hz. Nerve conduction studies and concentric needle electromyography were normal, and repetitive CMAPs to single nerve stimulation were not observed. Voluntary single fiber electromyography (SFEMG) showed increased jitter and blocking. Assessment of individual end-plates using SFEMG with intramuscular axonal microstimulation showed no uniform relationship between jitter and the rate of stimulation, consistent with a postsynaptic defect of neuromuscular transmission. Edrophonium eliminated the decremental response to repetitive nerve stimulation, but caused no significant clinical improvement, suggesting an additional mechanism for weakness in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cholinesterase Inhibitors / therapeutic use*
  • Edrophonium
  • Electromyography
  • Female
  • Genes, Recessive
  • Humans
  • Male
  • Myasthenia Gravis / congenital*
  • Myasthenia Gravis / drug therapy
  • Myasthenia Gravis / genetics
  • Neuromuscular Junction / physiology*
  • Receptors, Cholinergic / analysis
  • Roma
  • Synaptic Transmission / physiology*
  • Syndrome


  • Cholinesterase Inhibitors
  • Receptors, Cholinergic
  • Edrophonium