title: Presynaptic congenital myasthenic syndrome due to quantal release deficiency.
abstract: OBJECTIVE
  To provide clinical, electrophysiologic, and ultrastructural findings in three patients with a presynaptic congenital myasthenic syndrome (CMS).
  
  
  BACKGROUND
  Familial infantile myasthenia and paucity of synaptic vesicles are the only two fully characterized CMS. We are describing here three patients with another form of presynaptic CMS characterized by deficiency of the action potential-dependent release without reduction of the spontaneous release of neurotransmitter from the nerve terminal.
  
  
  METHODS
  The authors performed electromyography and anconeus muscle biopsies that included intracellular recordings and electron microscopy of the neuromuscular junction in three patients with presynaptic CMS. They also sequenced part of the P/Q-calcium alpha(1)-subunit gene (CACNA1A) and the acetylcholine receptor subunit (AChR) genes in these patients.
  
  
  RESULTS
  In these patients there were additional neurologic findings including nystagmus and ataxia. In all three patients the end-plate potential quantal content (m) was markedly reduced but neither the amplitudes nor the frequencies of miniature end-plate potentials were diminished. Ultrastructurally, postsynaptic end-plate folds, nerve terminal size, and synaptic vesicle number were normal but double-membrane-bound sacs containing synaptic vesicles were present in the nerve terminal of all three patients. The screening of reported pathogenic mutations in the CACNA1A and a mutational analysis of AChR subunit genes were negative.
  
  
  CONCLUSIONS
  This form of CMS appears to result only from a deficiency of the quantal release of neurotransmitter that may be due to an abnormal calcium mechanism or impaired endocytosis and recycling of synaptic vesicles.
authors.affiliation: Neurology Department, University of California, Davis 95616, USA. ramaselli@ucdavis.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Maselli
authors.forename: D Z
authors.initials: DZ
authors.lastname: Kong
authors.forename: C M
authors.initials: CM
authors.lastname: Bowe
authors.forename: C M
authors.initials: CM
authors.lastname: McDonald
authors.forename: W G
authors.initials: WG
authors.lastname: Ellis
authors.forename: M A
authors.initials: MA
authors.lastname: Agius
authors.forename: C M
authors.initials: CM
authors.lastname: Gomez
authors.forename: D P
authors.initials: DP
authors.lastname: Richman
authors.forename: R L
authors.initials: RL
authors.lastname: Wollmann
mesh_terms: D000293:Adolescent; D002648:Child; D004576:Electromyography; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009132:Muscles / Q000503:physiopathology; D020294:Myasthenic Syndromes, Congenital / Q000209:etiology* / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000503:physiopathology / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000172:deficiency*; D017729:Presynaptic Terminals / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents