A new case study was published in Cardiology Research and Practice. It reported a pathogenic RYR2 gene variant in a 9-year-old boy presenting with recurrent fainting episodes. The child had a family history of sudden cardiac death in a sibling and maternal episodes of syncope. Initial cardiac imaging and echocardiography were normal, with an ejection fraction of 60% and no structural abnormalities detected on MRI. However, electrophysiological studies revealed a QTc interval as high as 500 ms, raising suspicion for Long QT Syndrome (LQTS)

Whole-exome sequencing identified a heterozygous missense mutation, c.12370A>C (p.Ser4124Arg), in the RYR2 gene. This gene is typically linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), and it plays a crucial role in calcium regulation within heart muscle cells. In-silico analysis predicted the mutation to be pathogenic, and Sanger sequencing confirmed inheritance from the patient’s mother, who also experienced syncope.

The boy was treated with propranolol and remained symptom-free during an 18-month follow-up. This case demonstrates how RYR2 variants can contribute to atypical or overlapping arrhythmia phenotypes beyond CPVT, including presentations resembling LQTS. 

The findings emphasize the need for genetic screening in children with unexplained syncope and family histories of sudden cardiac death. Early identification of pathogenic variants not only clarifies diagnosis but also guides treatment strategies, such as beta-blocker therapy, which can be life-saving.