Skeletal-muscle channelopathies: periodic paralysis and nondystrophic myotonias.
Ključne riječi
Sažetak
OBJECTIVE
To provide a current review of clinical phenotypes, genetics, molecular pathophysiology, and electro-diagnostic testing strategies of periodic paralysis and nondystrophic myotonias.
RESULTS
The number of pathogenic mutations causing periodic paralysis and nondystrophic myotonias continues to increase. Important insight into the molecular pathogenesis of muscle sodium channelopathies has been revealed by the finding of 'leaky' closed sodium channels. Previously, alterations in sodium-channel activation or inactivation have been identified as important disease mechanisms. The recent discovery that substitutions of key arginine residues in the voltage-sensing segment of the channel may lead to a 'pore leak' when the channel is closed suggests a new mechanism. Since similar mutations exist in corresponding positions of other channels, this mechanism may apply to other channel diseases. The recognition of different electrophysiological patterns that are specific to muscle ion-channel genotypes will be useful in diagnosis and in guiding genetic testing. Recent studies demonstrate that magnetic resonance imaging may be used to detect intramuscular accumulation of sodium during episodes of weakness.
CONCLUSIONS
Recent advances have refined our ability to make a precise molecular diagnosis in muscle channelopathies. The description of a pore leak with voltage-sensor mutations may represent a new disease mechanism.
