Rhabdomyolysis and fluctuating asymptomatic hyperCKemia associated with CACNA1S variant

Eur J Neurol. 2018 Feb;25(2):417-419. doi: 10.1111/ene.13528. Epub 2017 Dec 26.

Abstract

Background and purpose: CACNA1S encodes Cav 1.1, a voltage sensor for muscle excitation-contraction coupling, which activates the ryanodine receptor 1 (RYR1) leading to calcium release from the sarcoplasmic reticulum. CACNA1S mutations cause hypokalemic periodic paralysis, malignant hyperthermia and congenital myopathy. RYR1 mutations result in congenital myopathy, malignant hyperthermia and rhabdomyolysis.

Methods: The aim was to describe a novel phenotype associated with a CACNA1S variant at a site previously linked to hypokalemic periodic paralysis.

Results: The patient presented with fluctuating asymptomatic creatine kinase elevation after an episode of rhabdomyolysis but has no history of periodic paralysis. His muscle biopsy showed core-like structures occurring mainly in type 2 fibers. He carries a novel Cav 1.1 variant (p.Arg528Leu) affecting a highly conserved amino acid. Different mutations at the same location cause hypokalemic periodic paralysis.

Conclusion: This case underscores the similarity between the phenotypes caused by mutations in two functionally linked proteins, RYR1 and Cav 1.1.

Keywords: CACNA1S; Cav1.1; cores; hyperCKemia; rhabdomyolysis.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Calcium Channels / genetics*
  • Calcium Channels, L-Type
  • Creatine Kinase / blood*
  • Humans
  • Male
  • Rhabdomyolysis* / blood
  • Rhabdomyolysis* / genetics
  • Rhabdomyolysis* / physiopathology

Substances

  • CACNA1S protein, human
  • Calcium Channels
  • Calcium Channels, L-Type
  • Creatine Kinase