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A newly recognized congenital myasthenic syndrome attributed to a prolonged open time of the acetylcholine‐induced ion channel
Author(s) -
Engel Andrew G.,
Lambert Edward H.,
Mulder Donald M.,
Torres Carlos F.,
Sahashi Ko,
Bertorini Tulio E.,
Whitaker John N.
Publication year - 1982
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410110603
Subject(s) - chemistry , neuromuscular junction , acetylcholine , endoplasmic reticulum , vacuole , biophysics , anatomy , acetylcholine receptor , myofibril , postsynaptic potential , endocrinology , neuroscience , biology , biochemistry , receptor , cytoplasm
Five familial cases (in two families) and one sporadic case of a new congenital myasthenic syndrome were investigated. Symptoms arise in infancy or later life. Typically, one finds selective involvement of cervical, scapular, and finger extensor muscles, ophthalmoparesis, and variable involvement of other muscles. There is a repetitive muscle action potential to single nerve stimulus in all muscles and a decremental response at 2 to 3 Hz stimulation in clinically affected muscles. Microelectrode studies reveal markedly prolonged end‐plate potential (epp), miniature end‐plate potential (mepp), and miniature end‐plate current; normal quantum content of the epp; and a smaller than normal or low‐normal mepp amplitude. Light microscopy demonstrates predominance of type I fibers, small groups of atrophic fibers, tubular aggregates and vacuoles near end‐plates, abnormal end‐plate configuration, and nonspecific myopathic changes. Abundant acetylcholinesterase activity is present at all end‐plates, and the activity and kinetic properties of this enzyme in muscle are normal. Calcium accumulated at the end‐plate in one patient. Quantitative electron microscopy shows decrease in the size of nerve terminals, increase in the density of synaptic vesicles, and reduction in the length of postsynaptic membranes. There is focal degeneration of junctional folds with corresponding loss of acetylcholine receptor, most marked in cases with the lowest mepp amplitude. There are no immune complexes at the end‐plate. Fiber regions near end‐plates display dilation, proliferation, and degeneration of the sarcoplasmic reticulum; nuclear, mitochondrial, and myofibrillar degeneration; and vacuoles resembling those found in periodic paralysis. A prolonged open time of the acetylcholine‐induced ion channel is considered to be the basic abnormality and may account for the physiological, morphological, and clinical alterations.