A rare case report of catecholaminergic polymorphic ventricular tachycardia with an uncommon CALM2 mutation.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a primary arrhythmia disorder characterized by syncope or sudden cardiac death and typically caused by a gain-of-function of the Ryanodine Receptor Type 2 ( RyR2 ) mutation. Calmodulin is a calcium-binding protein responsible for many intracellular signalling pathways and disruptions in function or regulation may lead to potentially fatal arrhythmias. We present a case of a young patient with CPVT found to have an unusual, potentially causative, Calmodulin 2-a protein coding gene ( CALM2 ) mutation.
Case Summary: A 21-year-old female with autism was brought to the ED following cardiac arrest. Bidirectional ventricular tachycardia was captured on electrocardiogram. Propranolol was initiated, and patient had no further episodes of ventricular arrhythmia. A subcutaneous implantable cardioverter defibrillator (ICD) was implanted, and further genetics testing was done. Rapid Whole Genome Sequencing (PGnome®-RAPID) resulted heterozygous variant of uncertain significance in CALM2 gene NM_001743.5 for variant c.136G>A.
Discussion: To the authors' knowledge, this is the third known record of such mutation in accordance with the International Calmodulin Registry ( n = 74). Identification of CALM mutations can help advance the understanding of genetic underpinnings of arrhythmias and underscore necessity of genetic screening and personalized treatment strategies. Subcutaneous ICDs offer a promising therapeutic option while minimizing risks associated with traditional transvenous ICDs.
Competing Interests: Conflict of interest: K.R.D., A.L.d.l.R., and S.S. have no conflicts of interest. D.D. has received consulting fees from Abbott® and speaking honorarium from Medtronic®.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)