Pleiotropic Phenotype of RYR2 Exon 3 Deletion: Biventricular Noncompaction and Malignant Arrhythmias

Pathogenic RYR2 variants cause a spectrum of inherited arrhythmia syndromes. The exon 3 deletion (E3DS) is a rare ryanodinopathy that combines arrhythmias and structural cardiomyopathy.

A 33-year-old woman was incidentally found to have premature ventricular contractions during pregnancy. Further evaluation revealed biventricular noncompaction, sinus node dysfunction, and nonsustained polymorphic ventricular tachycardia. In the postpartum, she developed persistent bradyarrhythmia. Electrophysiological study demonstrated complete supranodal atrioventricular block and extensive right atrial low-voltage areas. Cardiac magnetic resonance confirmed biventricular noncompaction. A dual-chamber implantable cardioverter-defibrillator was inserted; 3 months later, she experienced ventricular fibrillation terminated by appropriate implantable cardioverter-defibrillator shocks. Genetic testing identified a pathogenic RYR2 E3D (class 5) and a variant of uncertain significance in FLNC.

To our knowledge, this is the first reported case to demonstrate the complete phenotypic spectrum associated with RYR2 E3D.

E3DS should be suspected in patients presenting with a combination of conduction disease, atrial pathology, and left ventricular noncompaction.