Mutations in the Ras/mitogen activated protein kinase signaling pathways are known to be responsible for about 70% of NS cases.Persons with NS have up to a 50% chance of transmitting it to their offspring. The fact that an affected parent is not always identified for children with NS suggests several possibilities:

Manifestations could be so subtle as to go unrecognized (variable expressivity)
NS is heterogeneous, comprising more than one similar condition of differing causes, and some of these may not be inherited. A high proportion of cases may represent new, sporadic mutations.Heterozygous mutations in NRAS, HRAS, BRAF, SHOC2, MAP2K1, MAP2K2, and CBL have also been associated with a smaller percentage of NS and related phenotypes.A condition known as "neurofibromatosis–Noonan syndrome" is associated with neurofibromin. Diagnosis
NS can be confirmed genetically by the presence of any of the known mutations listed above. However, despite identification of 14 causative genes, the absence of a known mutation will not exclude the diagnosis, as  more, as-yet-undiscovered genes can cause NS. Thus, the diagnosis of NS is still based on clinical features. In other words, it is made when a physician feels that a person has enough of the features to warrant the label. The principal values of making a genetic diagnosis are that it guides additional medical and developmental evaluations, it excludes other possible explanations for the features, and it allows more accurate recurrence risk estimates.
Prognosis is therefore largely dependent on the presence or absence of cardiac disease, as well as the type and severity of the disease (if disease is present). Most notably, Noonan syndrome with hypertrophic cardiomyopathy is associated with increased mortality. History
Jacqueline Noonan was practicing as a pediatric cardiologist at the University of Iowa when she noticed that children with a rare type of heart defect, valvular pulmonary stenosis, often had a characteristic physical appearance, with short stature, webbed neck, wide spaced eyes, and low-set ears. Both boys and girls were affected. These characteristics were sometimes seen running in families but were not associated with gross chromosomal abnormalities. She studied 833 people with Noonan syndrome at the congenital heart disease clinic, looking for other congenital abnormalities, and, in 1963, presented a paper: "Associated non-cardiac malformations in children with congenital heart disease". This described 9 children who in addition to congenital heart disease had characteristic facial features, chest deformities and short stature. Dr. John Opitz, a former student of Dr. Noonans, first began to call the condition "Noonan syndrome" when he saw children who looked like those whom Dr. Noonan had described. Dr. Noonan produced a paper titled "Hypertelorism with Turner Phenotype" in 1968 where she studied 19 patients who displayed symptoms indicative of Noonans Syndrome. In 1971, at the Symposium of Cardiovascular defects, the name Noonan syndrome became officially recognized. References


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