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Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results.
- Source :
-
International journal of cardiology [Int J Cardiol] 2017 Oct 15; Vol. 245, pp. 92-98. Date of Electronic Publication: 2017 Jul 21. - Publication Year :
- 2017
-
Abstract
- Background: RASopathies are developmental disease caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. The aim of the present study was to provide a comprehensive description of morbidity and mortality in patients with molecularly confirmed RASopathy.<br />Methods: A multicentric, observational, retrospective study was conducted in seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to assess the impact of mutated genes on number of interventions and overall prognosis.<br />Results: Cardiac defects occurred in 80.3% of cases, almost half of them underwent at least one intervention. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10, and 20years, respectively. Restricted estimated mean survival at 20years follow-up was 19.6years. Ten patients died (2.7% of the entire cohort; 3.4% of patients with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age <2years or young adults, as well as subjects with biventricular obstruction and PTPN11 mutations had a higher risk of cardiac death.<br />Conclusions: The risk of intervention was higher in individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even though the specific association between HCM, biventricular outflow tract obstructions and PTPN11 mutations appeared to be associated with early mortality, including immediate post-operative events and sudden death.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Adolescent
Adult
Cardiomyopathy, Hypertrophic genetics
Cardiomyopathy, Hypertrophic mortality
Child
Child, Preschool
Female
Humans
Infant
Infant, Newborn
Middle Aged
Morbidity
Mortality trends
Noonan Syndrome genetics
Noonan Syndrome mortality
Protein Tyrosine Phosphatase, Non-Receptor Type 11 genetics
Pulmonary Valve Stenosis genetics
Pulmonary Valve Stenosis mortality
Retrospective Studies
Young Adult
Heart Defects, Congenital genetics
Heart Defects, Congenital mortality
MAP Kinase Signaling System genetics
Mutation genetics
ras Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1874-1754
- Volume :
- 245
- Database :
- MEDLINE
- Journal :
- International journal of cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 28768581
- Full Text :
- https://doi.org/10.1016/j.ijcard.2017.07.068