Introduction 1 PTPN11 2 PTPN11 25 6 KRAS BRAF MEK1 MEK2 7 8 Noonan syndrome 1 In most, the prenatal history is unremarkable but polyhydramnios is frequent. Height and weight are within normal limits at birth but height begins to drop off within a few months and over 70% of patients with NS have significantly short stature. Some patients with NS have significant feeding difficulties with resulting failure-to-thrive and require tube feedings. Although this may contribute to the poor gain in weight, short stature occurs equally in children who have no feeding problems in infancy. Other important findings include a chest deformity which may be in the form of a pectus carinatum or pectus excavatum, apparent widely spaced nipples and a relatively broad chest. Scoliosis and kyphosis occur in about 15% of patients. Muscle hypotonia is frequent and may account for some of the motor delay. Significant mental retardation is uncommon but some degree of learning disability is frequent and may require special help in school. Eye findings, especially strabismus and refractive errors are common and an occasional patient will have a coloboma. All children with NS should have a complete eye examination. Since conductive hearing loss is rather frequent, children should have a hearing evaluation. Over half of the males with NS have either one or both testes undescended and delay in puberty is common for both males and females. 9 10 2 PTPN11 Children with NS often present to the endocrinologists because of the short stature, delayed puberty or undescended testes in males. Although height and weight are usually in the normal range at birth, height drops off within the first few months. In general, there is at least a 2-year delay between bone age and chronological age. Continued growth may occur until the early 20s. In both males and females, there is a delay in puberty. Females seem to possess normal fertility. Males, as expected due to undescended testes, appear to have decreased fertility but male transmission is well described and not uncommon. 11 12 16 17 16 PTPN11 18 19 20 20 21 19 PTPN11 22 23 PTPN11 LEOPARD syndrome (LS) 3 24 25 PTPN11 20 Cardio-facio-cutaneous syndrome (CFC) 4 26 27 3 4 BRAF KRAS MEK1 MEK2 Costello syndrome 28 29 30 4 31 32 Conclusion 33 HRAS