Noonan syndrome is a genetically heterogeneous multiple malformation syndrome. It was formerly known as 'Turner-like syndrome' due to the similar phenotypic features of the two diseases. However, Noonan syndrome is associated with a normal karyotype, unlike the 45,XO karyotype of Turner's. The main features of this syndrome are webbed and short neck, down-slanting eyes, hypertelorism, strabismus, refractive errors, amblyopia, low-set ears, deeply grooved philtrum, micrognathia, abnormalities in the sternum like pectus excavatum, congenital heart disease, mental retardation in 25% cases, short stature, and delayed puberty.
Approximately 1 in every 1000 to 2500 live births is affected by Noonan syndrome. The disease affects people of all ethnicities and both the sexes equally. The inheritance of the disease has been seen to be either in an autosomal dominant fashion, or through sporadic mutations. Diagnosis of the disease involves evaluation of the physical features, katyotypic analysis to rule out Turner's syndrome, and gene tests for both the PTPN11 and KRAS genes. Treatment is mostly symptomatic. Growth hormone has been administered to accelerate growth in patients.
More than 50% of individuals affected with Noonan syndrome have been shown to have mutations in the Protein-Tyrosine Phosphatase, Nonreceptor-Type, 11 (PTPN11) gene. This gene maps to chromosome 12 and codes for a tyrosine phosphatase, the activity of which is important in signal transduction of cells, especially during the embryonic development of heart, blood cells, and other tissues. It also plays a pivotal role in cell movement, and cell specialization. Mutations in the gene lead to its constitutive activation and constitutive production of the protein, causing misregulation of cell division and growth.
Approximately 5-10% of patients with Noonan syndrome who do not have any mutations in the PTPN11 gene show mutations in the V-KI-RAS2 Kirsten Rat Sarcoma 2 Viral Oncogene Homolog (KRAS) gene. The protein product of this gene is also involved in the signal transduction in cells.