The Ryanodine Receptor 2 (RyR2) gene, located on chromosome 1q43, encodes the RyR2 protein. This protein, predominantly found in the sarcoplasmic reticulum (SR) of cardiomyocytes, acts as a Ca2+ release channel receptor, playing a crucial role in regulating Ca2+ release from the SR throughout the cardiac cycle [1]. Numerous mutations in the RyR2 gene have been associated with a broad range of heart diseases. In addition to cardiomyocytes, the RyR2 protein is also expressed in the brain, where it is involved in Ca2+ signaling and Ca2+ homeostasis [2,3].

In 2008, Lehnart et al. reported that mice heterozygous for the RyR2 R2474S mutation exhibited spontaneous generalized tonic-clonic seizures (GTCSs), exercise-induced ventricular arrhythmias, and sudden cardiac death [4]. In 2019, Yap et al. described a 32-year-old female who experienced three unprovoked GTCSs without arrhythmias over 12 years and was found to have the RyR2 mutation (c.229G > A/p.Ala77Thr) [5]. Her brother, carrying the same RyR2 mutation, exhibited symptoms of catecholaminergic polymorphic ventricular tachycardia (CPVT). In 2022, Hu et al. identified a novel RyR2 truncating mutation [c.12670G > T, p.(Glu4224*), NM_001035.3] in a 3-year-old child with focal epilepsy; the child's cardiac examination showed only sinus tachycardia and was otherwise unremarkable [6]. According to literature searches, various RyR2 gene mutations can lead to cardiac illness or epilepsy, yet no single RyR2 gene mutation has been linked to both malignant arrhythmias and epilepsy in the same patient.