Assessment of cardiac involvement in childhood neurofibromatosis type 1 diagnoses, identification of Rasopathic Cases

Abstract

This study aimed to investigate cardiac involvement in children and adolescents with neurofibromatosis type 1 (NF1), and to describe clinical correlates. Medical records of 114 NF1 patients (ages 1-18 years) followed at a tertiary center (2011–2017) were retrospectively reviewed. Among these patients, 58 (50.9%) underwent pediatric cardiology assessment with echocardiography (ECHO) and electrocardiography (ECG). ECHO abnormalities were defined a priori (valvular disease, septal hypertrophy, septal defects, and pulmonary valve stenosis); patent foramen ovale (PFO) was considered a normal variant. Demographics and NF1 features were compared between patients with and without cardiac pathology. Among the 58 evaluated patients, ECHO was abnormal in 18/58 (31.0%; 95% CI 20.6–43.8) and 1/58 (1.7%; 95% CI 0.3–9.1) had isolated ventricular extrasystoles, yielding 19/58 (32.8%; 95% CI 22.1–45.6) with any cardiac pathology. Valvular involvement occurred in 13/58 (22.4%; 95% CI 13.6–34.7); septal hypertrophy and septal defects each in 3/58 (5.2%; 95% CI 1.8–14.1); pulmonary valve stenosis in 1/58 (1.7%; 95% CI 0.3–9.1). No statistically significant difference in age, sex, or NF1 diagnostic features was observed between those with vs. without cardiac pathology (all p>0.05). Cardiac pathology was common among NF1 patients referred for cardiology evaluation, with valvular disease predominating. Given retrospective design and potential referral/selection bias, a routine baseline cardiology assessment at NF1 diagnosis appears reasonable, with a low threshold for follow‑up when symptoms, murmurs, or risk factors are present.