Skeletal muscle channelopathies: new insights into the periodic paralyses and nondystrophic myotonias.
OBJECTIVE
To summarize advances in our understanding of the clinical phenotypes, genetics, and molecular pathophysiology of the periodic paralyses, the nondystrophic myotonias, and other muscle channelopathies.


RESULTS
The number of pathogenic mutations causing periodic paralysis, nondystrophic myotonias, and ryanodinopathies continues to grow with the advent of exon hierarchy analysis strategies for genetic screening and better understanding and recognition of disease phenotypes. Recent studies have expanded and clarified the role of gating pore current in channelopathy pathogenesis. It has been shown that the gating pore current can account for the molecular and phenotypic diseases observed in the muscle sodium channelopathies, and, given that homologous residues are affected in mutations of calcium channels, it is possible that pore leak represents a pathomechanism applicable to many channel diseases. Improvements in treatment of the muscle channelopathies are on the horizon. A randomized controlled trial has been initiated for the study of mexiletine in nondystrophic myotonias. The class IC antiarrhythmia drug flecainide has been shown to depress ventricular ectopy and improve exercise capacity in patients with Andersen-Tawil syndrome.


CONCLUSIONS
Recent studies have expanded our understanding of gating pore current as a disease-causing mechanism in the muscle channelopathies and have allowed new correlations to be drawn between disease genotype and phenotype.
Platt
Daniel
D
University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA.
Griggs
Robert
R
D053447:Channelopathies / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007473:Ion Channels / Q000503:physiopathology*; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology; D020512:Myopathy, Central Core / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D020967:Myotonic Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D010245:Paralyses, Familial Periodic / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology
D007473:Ion Channels