Prevalence of Noonan spectrum disorders in a pediatric population with valvar pulmonary stenosis

Abstract

Objective:To evaluate the prevalence of Noonan spectrum disorders (NSD) in a pediatric population with valvar pulmonary stenosis (vPS) and identify the clinical characteristics that differentiate those with NSD from those without NSD.Design: A retrospective chart review of 204 patients diagnosed with vPS between 9/1/2012 and 12/1/2016 at a pediatric medical center was performed. The quantitative features of vPS, genetic diagnosis information, and phenotypic characteristics of Noonan syndrome were collected. Chi-square test, Fisher's exact test, t test, Wilcoxon rank-sum test, and ANOVA were used for comparisons among the groups.Logistic regression was used to test for the association between the clinical characteristics and the presence of NSD.Results: Syndromic diagnoses were made in 10% of the children with vPS, with NSD accounting for 6%. Hypertrophic cardiomyopathy (P < .0001), short stature (P < .0001), developmental delay (P < .0001), ophthalmological abnormalities (P < .0001), pectus carinatum/excavatum (P = .01), neurological abnormalities (P = .022), and aortic stenosis (P = .031) were present more often in individuals with NSD compared to nonsyndromic vPS. A logistic regression analysis showed a 4.8-fold increase in odds for NSD for each additional characteristic (P < .0001). Conclusions:At least 6% of the children with vPS have an underlying NSD. Individuals with vPS and NSD were significantly more likely to have additional features known to be associated with NSD than those with vPS without NSD. We conclude that vPS in the presence of one or more significant characteristics should prompt referral for genetic evaluation as a guide to ascertain patients at risk for NSD while optimizing the use of clinical genetics evaluation and potential genetic testing. K E Y W O R D Scongenital heart disease, pulmonary valve dysplasia, rasopathy | 265 ANDERSON et al.

Clinical and molecular analysis of 26 individuals with Noonan syndrome in a reference institution in Colombia

“…NS has a high phenotypic variability (Tartaglia et al, 2002) and can present with either isolated anomalies (pulmonary stenosis), minor facial features, short stature, or multiple congenital anomalies. The incidence of NS in individuals with pulmonary stenosis appears to be higher in the Colombian population when compared to other reports (Anderson et al, 2019).…”

Congenital heart defects in Noonan syndrome: Diagnosis, management, and treatment

“…In the context of CHD, the focus has been on patients with PVS as that is the commonest lesion. A study of a cohort of 204 patients with PVS found that 6% had NS (Anderson et al, ); of note, the cases with non‐syndromic PVS were not routinely tested for NS. Compared to non‐syndromic cases of PVS, those with PVS due to NS were more likely to have features associated with NS: short stature, pectus deformity, neurodevelopmental delays or other, unexpected cardiac issues such as HCM or AS.…”

“…In the context of CHD, the focus has been on patients with PVS as that is the commonest lesion. A study of a cohort of 204 patients with PVS found that 6% had NS (Anderson et al, 2019); of note, the cases with non-syndromic PVS were not routinely tested for Gene resequencing panels will become obsolete at some point. The cost of sequencing human exomes or genomes has declined spectacularly over the past several years (Sboner, Mu, Greenbaum, Auerbach, & Gerstein, 2011).…”

Genetic counseling for congenital heart disease – Practice resource of the National Society of Genetic Counselors

“…However, institutions may perform, or at least offer, a CMA to all individuals with complex/critical CHD regardless of the presence or absence of recognized syndromic features. (Anderson et al, 2019). Heterotaxy panels with the inclusion of primary ciliary dyskinesia genes should be considered in patients with complex cardiac defects such as unbalanced atrioventricular canal defects or malposed great vessels with or without additional left-right patterning abnormalities (Geddes et al, 2020;Pierpont et al, 2018).…”

“…Targeted multi‐gene panels commonly used for CHDs include RASopathy gene panels and heterotaxy gene panels. RASopathy gene panels should be considered in patients with features of Noonan‐spectrum disorders, valvar pulmonic stenosis with another cardiovascular malformation, or valvar pulmonic stenosis with specific extracardiac features (Anderson et al., 2019). Heterotaxy panels with the inclusion of primary ciliary dyskinesia genes should be considered in patients with complex cardiac defects such as unbalanced atrioventricular canal defects or malposed great vessels with or without additional left‐right patterning abnormalities (Geddes et al., 2020; Pierpont et al., 2018).…”