Cardiovascular disease in Noonan syndrome

被引:53
作者
Pierpont, Mary Ella [1 ,2 ]
Digilio, Maria Cristina [3 ]
机构
[1] Univ Minnesota, Dept Pediat, 2450 Riverside Ave, Minneapolis, MN 55454 USA
[2] Childrens Hosp Minnesota, Cardiovasc Res, Minneapolis, MN USA
[3] Bambino Gesu Pediat Hosp, Med Genet, Rome, Italy
关键词
congenital heart disease; hypertrophic cardiomyopathy; Noonan syndrome; RASopathy; OF-FUNCTION MUTATIONS; GENOTYPE-PHENOTYPE CORRELATIONS; ATRIOVENTRICULAR-CANAL DEFECT; CONGENITAL HEART-DEFECTS; GIANT CORONARY ANEURYSMS; PTPN11; GENE-MUTATIONS; HYPERTROPHIC CARDIOMYOPATHY; LEOPARD-SYNDROME; ACTIVATING MUTATIONS; MOLECULAR DIVERSITY;
D O I
10.1097/MOP.0000000000000669
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Purpose of review To provide information on the scope of cardiac disease in Noonan syndrome. Recent findings Noonan syndrome is a common autosomal dominant RASopathy disorder characterized by clinical findings of facial dysmorphism, congenital heart disease, and short stature. The degree of genetic heterogeneity has recently become evident in that Noonan syndrome is now known to be caused by mutations in a large variety of genes which produce dysregulation of the RAS-MAPK (mitogen-activated protein kinase) signaling pathway. The scope of cardiac disease in Noonan syndrome is quite variable depending on the gene mutation, with some mutations usually associated with a high incidence of congenital heart defects (PTPN11, KRAS, and others) while those with predominantly hypertrophic cardiomyopathy (HCM) have higher risk and morbidity profiles (RAF1, RIT1, and those associated with multiple lentigines). Summary Cardiac disease in Noonan syndrome varies according to the type of gene mutation. The most common forms of cardiac disease include pulmonary stenosis, HCM, and atrial septal defect. HCM in general is associated with increased risk, mortality, and morbidity. New concepts for potential treatments are discussed.
引用
收藏
页码:601 / 608
页数:8
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