Genotype-phenotype association by echocardiography offers incremental value in patients with Noonan Syndrome with Multiple Lentigines.

TitleGenotype-phenotype association by echocardiography offers incremental value in patients with Noonan Syndrome with Multiple Lentigines.
Publication TypeJournal Article
Year of Publication2020
AuthorsKauffman H, Ahrens-Nicklas RC, Calderon-Anyosa RJC, Ritter AL, Lin KY, Rossano JW, Quartermain MD, Banerjee A
JournalPediatr Res
Date Published2020 Dec 14
ISSN1530-0447
Abstract

BACKGROUND: Noonan Syndrome with Multiple Lentigines (NSML) and Noonan Syndrome (NS) can be difficult to differentiate clinically in early childhood. This study aims to describe characteristics of the ventricular septum that may differentiate NSML from NS. We hypothesize that the shape of the ventricular septum determined by echocardiography correlates with genotype and may distinguish patients with NSML from those with NS.

METHODS: We analyzed data from 17 NSML and 67 NS patients. Forty normal and 30 sarcomeric hypertrophic cardiomyopathy (HCM) patients were included as controls. Septal morphology was qualitatively evaluated, and septal angle was measured quantitatively at end diastole. We recorded the presence of a ventricular septal bulge (VSB) and reviewed genetic testing results for each patient.

RESULTS: The most important findings were a sigmoid septum (71%) and VSB (71%) in NSML. NSML septal angle was decreased compared to the normal and sarcomeric HCM control groups, respectively (149 ± 13 vs. 177 ± 3, p < 0.001; 149 ± 13 vs. 172 ± 7, p < 0.001). NS septal angle was similar to the controls (176 ± 6 vs. 177 ± 3, p > 0.5; 176 ± 6 vs. 172 ± 7, p > 0.5). NSML-linked pathogenic variants were associated with sigmoid septum and VSB.

CONCLUSIONS: These findings provide novel phenotypic evidence to clinicians that may offer incremental diagnostic value in counseling families in ambiguous NSML/NS cases.

IMPACT: Characteristics of the ventricular septum are linked to specific gene variants that cause NSML and NS. Sigmoid septum and VSB are associated with NSML. This novel echocardiographic association may help clinicians distinguish NSML from NS in ambiguous cases. Early distinction between the two may be important, as syndrome-specific therapies may become available in the near future. This study may encourage further research into genotype-phenotype associations in other forms of HCM.

DOI10.1038/s41390-020-01292-7
Alternate JournalPediatr Res
PubMed ID33318624