Mutations of Shp2 give rise to many distinct human diseases: Germ line Shp2 mutations result in Noonan Syndrome (NS), one of the most common autosomal dominant disorders, and LEOPARD Syndrome (LS), known, as its acronym reminds us, for its major manifestations: multiple Lentigines, Electrocardiographic aberrations, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, and sensorineural Deafness [153, 154]. Here, PTPN11 is linked to Noonan syndrome with multiple lentigines.