Autosomal Recessive Atrial Dilated Cardiomyopathy Due to NPPA Mutation in a Young Patient

TL;DR

A young patient with a rare NPPA gene mutation developed atrial cardiomyopathy and atrial fibrillation, highlighting the need for genetic testing in similar cases.

Contribution

This case report presents a rare autosomal recessive NPPA mutation causing atrial cardiomyopathy in a young patient.

Findings

The patient was homozygous for the NPPA c.449G>A (p.Arg150Gln) variant and developed atrial fibrillation at age 18.

Genetic testing in young patients with atrial fibrillation may aid in early diagnosis of NPPA-related cardiomyopathy.

Anticoagulation is recommended for NPPA-related ADCM due to high thromboembolic risk despite low clinical scores.

Abstract

Background: Atrial dilated cardiomyopathy (ADCM) related to homozygous Natriuretic Peptide Precursor A (NPPA) pathogenic variants is an exceptionally rare inherited atrial cardiomyopathy characterized by progressive atrial enlargement, supraventricular arrhythmias, and eventual atrial standstill. Case summary: We report the case of a 9-year-old girl identified through population genetic screening as a homozygous carrier of the NPPA c.449G>A (p.Arg150Gln) variant who subsequently developed symptomatic paroxysmal atrial fibrillation (AF) at the age of 18. Although baseline cardiac investigations were normal, her current evaluation shows biatrial enlargement with preserved ventricular function. She underwent radiofrequency pulmonary vein isolation; however, recurrent symptomatic AF persists, requiring ongoing antiarrhythmic therapy and long-term oral anticoagulation (CHA2DS2-VA: 0; HAS-BLED: 0). Notably, patients with NPPA-related ADCM have a markedly increased thromboembolic risk due to progressive atrial mechanical failure, and anticoagulation should therefore be considered irrespective of conventional clinical risk scores. Discussion and conclusions: This case highlights the importance of genetic testing in young patients with atrial fibrillation and no underlying structural heart disease. The early identification of NPPA-related atrial dilated cardiomyopathy may aid in risk stratification and guide rhythm and anticoagulation management. Expanding genetic screening in select individuals with isolated atrial fibrillation may facilitate earlier diagnosis in this exceptionally rare condition.

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