Abstract 16401: Defining the Cardiovascular Genotype-Phenotype Correlations in Noonan Syndrome.
Aim: To describe the spectrum of heart disease in a large genotypically- and phenotypically-defined cohort of patients with Noonan syndrome.
Method: An international research database of patients with Noonan syndrome was combined with the medical records of all clinically-defined Noonan syndrome patients at Children's Hospital Boston and reviewed for structural heart disease. Noonan syndrome gene mutations in PTPN11, RAF1, SOS1, SHOC2, KRAS and/or BRAF were screened for in 74.5% of the cohort.
Results: A total of 294 patients were identified with Noonan syndrome. Cardiac lesions noted included pulmonary stenosis (56.8%) atrial septal defect (32.3%), hypertrophic cardiomyopathy (16.7%), ventricular septal defect (11.9%), patent ductus arteriosus (8.8%), aortic root dilation (4.8%), aortic coarctation (2.4%) and tetralogy of fallot (1.7%). No structural heart disease was seen in 19% of patients. Of those with pulmonary stenosis, 25.7% had the valve balloon dilated in the cardiac catheterization laboratory and 35.3% underwent operative repair. 48.8% of the patients undergoing pulmonary valve balloon dilation went on to require a surgical repair. Atrial septal defects were surgically closed in 53.7% and catheter-device occluded in 4.2%. Patent ductus arterioses were surgically ligated or coil-occluded in 38%. Of those patients with hypertrophic cardiomyopathy, 10% underwent operative palliation. Overall mortality rate for hypertrophic cardiomyopathy was 14% at a mean age of 10.6 years old. Pericardial effusions or late-onset pleural effusions were seen in 6% of all patients undergoing surgery. Mutations were identified in the genes PTPN11 (40.6%), SOS1 (11.4%), BRAF (3.6%), RAF1 (3.2%), SHOC2 (1.4%) and KRAS (1.4%). Significant associations were identified between gene mutations in PTPN11 and pulmonary stenosis (p<0.001), PTPN11 and atrial septal defects (p=0.001), and RAF1 and hypertrophic cardiomyopathy (p<0.001).
Conclusion: This report describes the largest cohort of phenotypically- and genotypically-defined patients with Noonan syndrome in the literature. The surgical management, survival & genotype-phenotype correlations in Noonan syndrome are defined.
- © 2010 by American Heart Association, Inc.