Cipriani, Marina

Background and purposeCACNA1S encodes Cav1.1, 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.MethodsThe aim was to describe a novel phenotype associated with a CACNA1S variant at a site previously linked to hypokalemic periodic paralysis.ResultsThe 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 Cav1.1 variant (p.Arg528Leu) affecting a highly conserved amino acid. Different mutations at the same location cause hypokalemic periodic paralysis.ConclusionThis case underscores the similarity between the phenotypes caused by mutations in two functionally linked proteins, RYR1 and Cav1.1.