Cognitive and autonomic dysfunction associated with a novel RYR2 variant: A case report

Abstract

Variants in the ryanodine receptor 2 (RYR2) gene are primarily associated with catecholaminergic polymorphic ventricular tachycardia. However, recent studies have also identified potential links to neurological pathologies, including Alzheimer’s disease, benign epilepsy of childhood, and neurodevelopmental disorders. Despite these findings, there is limited data on the association between RYR2 variants and additional neurological symptoms, such as autonomic dysfunction. This case report describes the clinical progression of a father-son pair, who carry a novel pAsn2517Ser variant in the RYR2 gene, identified through genetic studies. The report highlights distinct neurological manifestations in both individuals: the father exhibited Alzheimer’s-like cognitive dysfunction, while the son presented with an autonomic disorder. This case aims to provide additional information on the role of RyR2 in the brain and the symptomatology associated with pathological variants. Given that both father and son share the same RYR2 mutation, the observed neurological manifestations are likely attributable to this genetic alteration. These cases offer novel clinical insights into the role of cytoplasmic calcium regulators and their impact on the neurological system.