Hypokalemic periodic paralysis associated with the atypical CACNA1S c.2690G>A (p.Arg897Lys) variant : description of 14 affected individuals from five families

Abstract

Altres ajuts: acords transformatius de la UAB

This study describes five families (14 individuals) with hypokalemic periodic paralysis carrying a heterozygous pathogenic variant NM_000069.3:c.2690G>A (p.Arg897Lys) in the Calcium Voltage-Gated Channel Subunit Alpha1 S (CACNA1S) gene. The clinical exam showed pelvic weakness was common (10/14, with three being too young to exclude this age-dependent myopathy). Electromyography showed myogenic changes, and the long exercise test did not reveal a significant reduction of compound muscle action potential amplitude. Muscle MRI in three patients demonstrated involvement of axial musculature, the pelvic girdle, thighs (with relative sparing of sartorius and gracilis), and legs (especially the gastrocnemius muscles). A homozygosity haplotype analysis in three families revealed a shared segment of approximately 10 million base pairs, suggesting a common ancestor 2-8 generations ago.