To provide information on the scope of cardiac disease in Noonan syndrome.
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).
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.
aDepartment of Pediatrics, University of Minnesota
bCardiovascular Research, Children's Hospital of Minnesota, Minneapolis, Minnesota, USA
cMedical Genetics, Bambino Gesù Children's Hospital, Rome, Italy
Correspondence to Mary Ella Pierpont, MD, PhD, Department of Pediatrics, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, USA. Tel: +1 612 626 9784; fax: +1 612 625 0500; e-mail: firstname.lastname@example.org