To investigate the prevalence of Noonan spectrum disorders in a pediatric population with pulmonary valve stenosis (PVS) and explore other characteristics of NSD associated with PVS.
A retrospective medical record review was completed for patients with a diagnosis of PVS seen at the Children’s Hospital Colorado Cardiology clinic between 2009 and 2019. Syndromic diagnoses, genotypes, cardiac characteristics and extra-cardiac characteristics associated with NSD were recorded; statistical analysis was conducted using R.
Syndromic diagnoses were made in 16% of 686 pediatric patients with PVS, with NSD accounting for 9% of the total diagnoses. Individuals with NSD were significantly more likely to have atrial septal defect (ASD) and/or hypertrophic cardiomyopathy (HCM) than the non-NSD individuals. Supravalvar pulmonary stenosis (SVPS) was also significantly correlated with NSD. Extracardiac clinical features presenting with PVS that were significantly associated with NSD included feeding issues, failure to thrive, developmental delay, short stature, and ocular findings. The strongest predictors of NSD diagnosis were cryptorchidism (70%), pectus abnormalities (66%) and ocular findings (48%). The presence of a second characteristic further increased this likelihood, the highest probability occurring with cryptorchidism combined with ocular findings (92%).
The 9% prevalence of NSD in patients with PVS should alert clinicians to consider NSD when encountering a pediatric patient with PVS. The presence of PVS with one or more NSD-related features should prompt a genetics evaluation and genetic testing for RAS pathway defects. NSD should also be included in the differential when a patient presents with SVPS.

Copyright © 2021. Published by Elsevier Inc.