CACNA1S and periodic paralysis: An individual homozygous for p.R1451L had more frequent and severe episodes of weakness, one of which with serum K+ 2.8 mM was suggestive of HypoPP.21 Expression studies of R1451L did not reveal a gating pore leakage current—the canonical defect in HypoPP—but instead showed LOF changes (reduced peak current and enhanced inactivation) that may cause this unusual form of periodic paralysis in homozygous patients.21 Unlike the cases herein, however, the LOF aspects of the mixed channel defects for p.R1451L did not result in a CMS syndrome in the homozygous proband.