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This Article Figures Only Full Text Full Text (PDF) Data Supplement All Versions of this Article: 01.wnl.0000205596.19540.2cv1 66/8/1223    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Milone, M. Articles by Engel, A. G. Search for Related Content PubMed PubMed Citation Articles by Milone, M. Articles by Engel, A. G. Related Collections Myasthenia

Novel congenital myasthenic syndromes associated with defects in quantal release

From the Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN.

Address correspondence and reprint requests to Dr. Andrew G. Engel, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905; e-mail: age{at}mayo.edu

Background: Most congenital myasthenic syndromes are caused by defects in postsynaptic or synaptic basal lamina–associated proteins; congenital myasthenic syndromes (CMSs) associated with presynaptic defects are uncommon. Here, the authors describe clinical, electrophysiologic, and morphologic features of two novel and highly disabling CMSs, one determined by presynaptic and the other determined by combined presynaptic and postsynaptic defects.

Methods: Microelectrode, single channel patch clamp, immunocytochemical, [¹²⁵I]-bungarotoxin binding, and quantitative electron microscopy studies of endplates were performed. Candidate genes were directly sequenced.

Results: Patient 1, a 7-year-old boy, had severe myasthenic symptoms since infancy. Patient 2, a 48-year-old man, had delayed motor milestones and became progressively weaker after age 2 years. Both used wheelchairs and had a 30-50% EMG decrement on 2-Hz stimulation. Evoked quantal release was reduced to approximately 25% of normal in both. In Patient 2, the synaptic response to acetylcholine was further compromised by degeneration of the junctional folds with concomitant loss of the acetylcholine receptor (AChR). A search for mutations in components of the synaptic vesicle release complex and in other candidate proteins failed to identify the molecular basis of the two syndromes.

Conclusions: Combined clinical, morphologic, and in vitro electrophysiologic findings define two novel congenital myasthenic syndromes. The molecular basis of these syndromes awaits discovery.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 25 issue to find the title link for this article.

This article was previously published in electronic format as an Expedited E-Pub on March 8, 2006, at www.neurology.org.

Supported by NIH grant NS6277 and a research grant from the Muscular Dystrophy Association.

Disclosure: The authors report no conflicts of interest.

Received October 7, 2005. Accepted in final form January 13, 2006.