Noonan syndrome is one of the most common causes of human congenital heart disease and is frequently associated with missense mutations in the protein phosphatase SHP-2.
After PTPN11 was identified as a Noonan syndrome disease gene, additional discoveries have made clear that mutations in other genes along the RAS signaling pathway can cause a spectrum of syndromes and possibly isolated congenital heart disease.
Finally, mutations in the Ptpn11 gene (encoding SHP-2) underlie the developmental disorders Noonan syndrome and Leopard syndrome characterized by congenital heart disease and hematologic abnormalities.