Noonan syndrome (NS, https://omim.org/entry/163950) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002).
Genetic Heterogeneity of Noonan Syndrome
See also NS3 (609942), caused by mutation in the KRAS gene (190070); NS4 (610733), caused by mutation in the SOS1 gene (182530); NS5 (611553), caused by mutation in the RAF1 gene (164760); NS6 (613224), caused by mutation in the NRAS gene (164790); NS7 (613706), caused by mutation in the BRAF gene (164757); NS8 (615355), caused by mutation in the RIT1 gene (609591); NS9 (616559), caused by mutation in the SOS2 gene (601247); and NS10 (616564), caused by mutation in the LZTR1 gene (600574).
See also NS2 (605275) for a possible autosomal recessive form of NS; Noonan syndrome-like disorder with loose anagen hair-1 (NSLH1; 607721), caused by mutation in the SHOC2 gene (602775); Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2; 617506), caused by mutation in the PPP1CB gene (600590); and Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL; 613563), caused by mutation in the CBL gene (165360).
Mutations in the neurofibromin gene (NF1; 613113), which is the site of mutations causing classic neurofibromatosis type I (NF1; 162200), have been found in neurofibromatosis-Noonan syndrome (NFNS; 601321).