Expanding the Ryr2 Phenotypic Spectrum: Long Qt Syndrome and Left Ventricular Noncompaction in a Pediatric Patient

Background Genetic cardiac overlap syndromes pose significant diagnostic and therapeutic challenges in pediatric patients, particularly when arrhythmogenic and structural phenotypes coexist. Variants in the RYR2 gene are classically associated with catecholaminergic polymorphic ventricular tachycardia and arrhythmogenic cardiomyopathy; however, their involvement in complex phenotypes including long QT syndrome (LQTS) and left ventricular noncompaction (LVNC) remains poorly defined. Case presentation We report the case of a 10–year–old boy with incidental detection of QTc prolongation during antibiotic therapy. Although initially considered drug–related, repeat electrocardiography one month later confirmed persistent QTc prolongation up to 480 ms. Cardiac evaluation revealed a globular left ventricle with prominent mid–apical trabeculations, consistent with early–stage LVNC, and preserved systolic function. Cardiac magnetic resonance imaging confirmed LVNC in the absence of myocardial fibrosis or edema. Holter monitoring documented mean QTc values between 460 and 480 ms and a short run of non–sustained ventricular tachycardia. Genetic testing identified a heterozygous de novo RYR2 variant of uncertain significance, with no pathogenic variants detected in genes classically associated with LQTS or LVNC. Beta–blocker therapy was initiated, resulting in QTc normalization (∼440 ms) and no arrhythmic events during follow–up. Continuous rhythm surveillance was ensured by an implantable loop recorder. Conclusions This case describes a rare pediatric cardiac overlap phenotype combining LQTS and LVNC in association with an RYR2 variant, suggesting a possible pleiotropic effect of this gene. Careful longitudinal follow–up and prolonged rhythm monitoring are essential for risk stratification and for guiding therapeutic decisions, including consideration of implantable cardioverter–defibrillator therapy.