Skeletal muscle channelopathies: nondystrophic myotonias and periodic paralysis

Abstract

Recent discoveries in the skeletal muscle channelopathies have increased our understanding of the genetics and pathophysiology of these diseases. Studies reporting imaging techniques raise the possibility of improved disease monitoring and better outcome measures for clinical trials. Randomized controlled trials to establish an evidence base upon which to recommend standard treatments are required.

Mutations of SCN4A gene cause different diseases: 2 case reports and literature review

“…3 Our proband never complained of exacerbation by potassium-rich foods or drugs and only performed transient periodic paralysis following stiffness triggered by cold or movement stimulus. Although phenotype of the proband was characterized by a mild myotonia with cold sensitivity and without common performance of paramyotonia, we tend to consider the probable diagnosis as paramyotonia.…”

“…It is characterized by episodes of flaccid paralysis in association with low serum potassium. 3 Interestingly, all the documented mutations for hypoPP2 are at arginine residues of the voltage sensor S4 of domains in SCN4A, especially in domain II. 4 PMC is inherited autosomal-dominantly and is characterized by muscle stiffness exacerbated by cold and exertion.…”

Novel Insights into the Pathomechanisms of Skeletal Muscle Channelopathies

“…In hypokalemic periodic paralysis (HypoPP) myotonia is not observed [5] and muscle fibers are abnormally sensitive to low extracellular potassium concentrations, which (paradoxically) also lead to muscle fiber depolarization [6••]. The last few years have seen exciting advances in our understanding of HypoPP pathomechanisms [6••, 7•, 8], although the origin of the very marked hypokalemia that develops during attacks remains unclear.…”

Effect of mexiletine on transitory depression of compound motor action potential in recessive myotonia congenita

“…NDM are characterized by two contrasting phenomena: abnormal membrane over-excitation resulting in muscle stiffness (myotonia) and muscle inexcitability clinically manifesting as flaccid paralysis (periodic paralysis) or transient weakness (Matthews et al, 2010;Mankodi and Thornton, 2002;Raja Rayan and Hanna, 2010). Periodic palsy, when associated with myotonia, is usually indicative of a sodium channel dysfunction, while myotonia plus transient weakness (TW) strongly suggests a chloride channel dysfunction (Trip et al, 2009;Raja Rayan and Hanna, 2010 TW occurs at the beginning of a voluntary muscle contraction and quickly vanishes.…”

“…Periodic palsy, when associated with myotonia, is usually indicative of a sodium channel dysfunction, while myotonia plus transient weakness (TW) strongly suggests a chloride channel dysfunction (Trip et al, 2009;Raja Rayan and Hanna, 2010 TW occurs at the beginning of a voluntary muscle contraction and quickly vanishes. It is easily masked by the overlapping myotonia, and is thus rarely reported as a symptom, which renders its clinical appreciation quite difficult even for qualified clinicians.…”