Noonan Syndrome (male Turner syndrome, female pseudo-Turner syndrome, 12q24.1)

Noonan syndrome is apparently caused by an autosomal dominant gene with an incidence of 1–2.5 × 10⁻³. It is about twice as common among male than female offspring. Noonan mutations were assigned to human chromosomes 17q, 22q, and 12q224.1 but the identification is hampered by the variable penetrance. The SHP2/PTPN11 gain of function mutations enhance calcium oscillations and impair NFAT signaling (Uhlén P et al 2006 Proc Natl Acad Sci USA 103:2160). PTN11, KRAS, and SOS1 are responsible for 60% of Noonan cases. The symptoms are variable and complex yet there is some resemblance to females with Turner syndrome; but Noonan also affects males. Short stature, a webbed neck, mental retardation, heart and lung defects (stenosis), cryptorchidism, etc.—without visible chromosomal abnormalities—frequently accompany it. Cystic hygroma (lymphangioma) or nuchal lucency (shiny outgrowth on the back of the neck) may be detected by fetal ultrasonography. Missense mutation in the PTPN11 gene encoding...