NPPA-Associated Atrial Dilated Cardiomyopathy: Genotypic and Phenotypic Insights From an Ultrarare Inherited Disorder

Background: Atrial standstill is a rare arrhythmogenic disorder characterized by complete atrial electrical and mechanical inactivity. We report the 15th documented case of atrial dilated cardiomyopathy associated with the homozygous c.449G>A (p.Arg150Gln) NPPA mutation. Case summary: A 31-year-old woman presented with persistent atrial fibrillation, biatrial enlargement, and junctional rhythm. Electrophysiological studies confirmed atrial inexcitability. Despite preserved ventricular function, she required permanent His-bundle pacing. Genetic testing later revealed a homozygous NPPA mutation, whereas heterozygous family members remained asymptomatic. Discussion: This case highlights the diagnostic value of genetic testing in young patients with atrial fibrillation and no structural heart disease. Early recognition of NPPA-related atrial dilated cardiomyopathy may guide arrhythmia management and anticoagulation strategies, reducing thromboembolic risk. Take-home message: Broader implementation of genetic screening in selected individuals with isolated atrial dysfunction may support earlier diagnosis, personalized treatment, and better outcomes in this ultrarare condition.