O1006: Characterization of arrhythmias and electrocardiographic abnormalities in pediatric patients with RASopathies

Background: RASopathies, including Noonan syndrome (NS), are genetic syndromes with known cardiac manifestations including hypertrophic cardiomyopathy (HCM) and valve abnormalities; however, there is limited data on electrophysiologic abnormalities. This knowledge gap is reflected in current RASopathy management guidelines with limited information on electrophysiologic surveillance. This study aimed to characterize arrhythmias and ECG findings in a pediatric RASopathy population.

Methods: This was a single-center retrospective cohort study. Participants 0-18 years of age with a genetic diagnosis of a RASopathy syndrome followed at SickKids Hospital between 2001-2023 were included. Patients without cardiac testing (i.e. echocardiogram, ECG) performed were excluded. Descriptive statistics was used to characterize participants including type of arrhythmias, ECG abnormalities, and anti-arrhythmic therapies.

Results: Seventy-six participants were included in this study. Sixty-seven (88%) had NS, 7 (9.2%) had NS with multiple lentigines, and 2 (2.6%) had another RASopathy syndrome. Sixty-two (82%) had congenital heart disease (CHD), 25 (33%) had HCM, and 62 (82%) had non-cardiac co-morbidities. Abnormal ECG findings included 45 participants (61%) with any axis deviation, 34 (46%) with a bundle branch block or nonspecific interventricular conduction delay, and 44 (59%) with QTc prolongation. Of those with abnormal ECG findings, 4 (5.4%) did not have CHD or HCM. Five (6.6%) participants experienced arrhythmia(s), all of which had either CHD or HCM. Types of arrhythmias included atrial flutter (n=3), atrial fibrillation (n=1), ectopic atrial tachycardia (n=3), ventricular tachycardia (n=3), and ventricular fibrillation (n=2).

Conclusion: Electrophysiologic abnormalities are common in RASopathy patients with heart disease, with almost two-thirds having at least one ECG abnormality. Arrhythmias occurred less frequently; however, this may be underrepresented due to practice variability in arrhythmia screening in this patient population. Future directions include exploring the impact of ECG abnormalities and arrhythmias on health outcomes, such as hospitalizations, electrophysiologic interventions, medication use, and transplant-free survival.