Importance of school electrocardiogram screening and genetic testing in pediatric patients for early diagnosis of arrhythmogenic right ventricular cardiomyopathy

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by right ventricular structural changes and ventricular arrhythmias (VAs). It is mainly caused by pathogenic variants in desmosomal genes. ARVC typically presents in adults aged 20 to 50 years and is less commonly observed in children. Therefore, the clinical characteristics of pediatric ARVC patients remain poorly understood.

Purpose

We aimed to characterize phenotypes and genotypes in pediatric patients with ARVC and compare them with those of adult patients.

Methods

This study consisted of 181 Japanese ARVC probands who underwent genetic testing from 2005 to 2025 and were diagnosed with definite ARVC by 2010 Task Force Criteria (TFC2010). We divided the probands into two groups based on age at diagnosis: pediatric probands (<18-year-old, n=22) and adult probands (≥18-year-old, n=159). The age of 18 is legally recognized as adulthood in Japan.

Results

As shown in Figure 1-A, the primary reason for visiting medical institutions among pediatric probands was an abnormal electrocardiogram, including premature ventricular contractions and inverted T waves in broad leads, detected by heart disease screening in schools (n=16, 73%). Fewer pediatric probands presented with cardiac symptoms at initial presentation than adults (20% vs. 49%, p=0.017). The presence of epsilon waves was less common in pediatric probands than adults (23% vs. 52%, p=0.03). There were no significant differences in right ventricular structural alterations detected by imaging between the two groups.

Event-free survival for lethal VAs within 5 years from the initial presentation—including ventricular fibrillation, sudden cardiac death, and appropriate implantable cardioverter defibrillator therapy—was almost the same in pediatric probands compared to adults (Log-rank test: p=0.737) (Figure 1-B).

In the genetic testing, pediatric probands carried pathogenic variants more frequently than adult ones [n=20 (91%) vs. n=108 (68%), p=0.026]. The detection rate of pathogenic variants tended to decline with age (Figure 2-A). As shown in Figure 2-B, biallelic DSG2 variants were the most common among pediatric probands, followed by variants in multiple genes and PKP2 variants. Five pediatric probands reached TFC2010 Definite thanks to the positive genetic test.

Conclusions

Even though most of the pediatric ARVC probands were asymptomatic, the incidence of lethal VA in them was comparable to that in adults. Electrocardiograms at heart disease screening in schools and genetic testing facilitate the early diagnosis of ARVC in pediatric patients, which would help to prevent sudden cardiac death in the young.Figure1Figure2