Abnormal Growth in Noonan Syndrome: Genetic and Endocrine Features and Optimal Treatment

Noonan syndrome (NS) is a phenotypically heterogeneous syndrome which is frequently associated with short stature. Recent genetic investigations have identified mutations in five genes, namely PTPN11, KRAS, SOS1, NF1 and RAF1 in patients with the NS phenotype. PTPN11 is the commonest, being present in approximately 50% of cases. The degree of short stature in children does not associate closely with the presence of mutations, however some PTPN11-positive patients have decreased GH-dependent growth factors consistent with mild GH insensitivity. GH therapy, using doses similar to those approved for Turner syndrome (TS), induced short-term increases in height velocity over 1-3 years, and may improve final adult height with longer-term treatment.