SCIENTIFIC BACKGROUND

CACNA1S, CLCN1, HSPG2, KCNJ2, SCN4A

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Scientific Background

Pathogenic variants in different ion channel genes cause the so-called “skeletal muscle canalopathies”. These represent a group of rare neuromuscular diseases. The ion channels affected include various cations (sodium, potassium, calcium) or anions (chloride), which play an important role in depolarization of the muscle membrane. Skeletal muscle channelopathies are broadly divided into two main categories:

 

  • 1. non-dystrophic myotonias: Thomsen and Becker (chloride channel myotonias), paramyotonia congenita and other sodium channel myotonias (due to pathogenic variants of the SCN4A gene) and
  • 2. the most important forms of periodic paralysis in terms of differential diagnosis. In contrast to the most frequently occurring myotonic dystrophy (Curschmann-Steinert), these are rare diseases that do not lead to muscular dystrophy.

 

The clinical characteristic of non-dystrophic myotonia is the manifestation of myotonia, an involuntary temporary contraction of skeletal muscle. Periodic paralyses are characterized by episodic muscle weakness. The clinical manifestation depends on the “net effect” of depolarization on the muscle membrane, which may be more or less excitable.

 

The diseases begin in childhood or at birth (paramyotonia congenita). Since there are different triggering factors and prophylactic or therapeutic approaches, a clear diagnosis should be sought; panel diagnostics can be helpful here.

 

Myotonias, non-dystrophic

Genes: CLCN1, HSPG2, SCN4A

 

Hypokalemic periodic paralysis (HypoPP)

Genes: CACNA1S, KCNJ2, SCN4A

 

References

Al-Ghamdi et al. 2017, Ped Neurol doi: 10.1016/ / Trivedi et al. 2014, Exp Neurol, 253:28 / Matthews et al. 2010, Brain 133:9

GENES

CACNA1S, CLCN1, HSPG2, KCNJ2, SCN4A
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