[II-JCKAP1-2] Calmodulinopathy in Japanese Children - Their Cardiac Phenotypes Are Severe and Show Early Onset in Fetal Life and Infancy
キーワード：Calmodulinopathy, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia
Calmodulinopoathy is a new disease entity caused by variants in genes encoding calmodulin and leading to sudden cardiac death due to lethal arrhythmias. Calmodulin has four Ca2+ binding sites and binds to proteins which have no Ca2+ binding site. Interestingly, calmodulin is encoded by three different genes: CALM1, CALM2 and CALM3, it means that calmodulin is an indispensable protein for species. Two CALM1 variant, p.N53I and p.N97S (amino acids number was corrected as N98S afterwards) were first identified in a family with catecholaminergic polymorphic ventricular tachycardia (CPVT) in 2012. Then, several variants in CALM1, CALM2 and CALM3 have been identified in patients with inherited arrhythmias including LQTS, and most of the variants locate at the Ca2+ binding sites. We recently identified 10 pediatric patients with carmodulinopathy out of 195 symptomatic children (aged 0-12) who were suspected as LQTS/CPVT but not identified pathogenic variants in related genes except for CALM1-3. Two patients carried variants in CALM1 and others in CALM2. We could perform familial screening in 8 patients and found all the variants were de novo ones. Two infants with severe LQTS phenotype died within 1 year after birth. Five patients who showed phenotype of LQTS or CPVT or both suffered cardiac arrest, and 1 LQTS patients experienced syncope. Two CPVT patients with developmental delay carried a same CALM2 variant, p.E46K. Although calmodulinopathy is a very rare disease, we should not overlook the disease to prevent unexpected sudden cardiac death, especially in children.