Noonan syndrome is an autosomal dominant genetic condition characterized by distinctive facial features, short stature, cardiac defects, coagulopathy, skeletal abnormalities, and normal to mild cognitive impairment. In most affected individuals, it is a result of mutations in one or more of the following genes: PTPN11, SOS1, KRAS, BRAF, NRAS, RAF1, MEK1.
Individuals with Noonan syndrome have abnormal facial features, congenital heart disease, short stature, and chest deformity . Skeletal, genitourinary, neurologic, lymphatic, and eye findings may also be present. Abnormal facial features include a deep groove in the area between the mouth and nose (philtrum), widely spaced eyes that are strikingly blue or blue-green in color, low-set ears, and short, and webbed neck . Coagulation disorders are present in half of people with Noonan syndrome; affected individuals may report excessive bruising, nosebleeds, or excessive bleeding upon an injury or surgery. Less often, women with Noonan syndrome will present with menorrhagia (excessive bleeding) during menstruation . Cryptorchidism (undescended testes) and infertility in males have been associated with Noonan syndrome. Affected individuals may have cognitive impairment. Cognitive impairment may include low to average intelligence, slower processing speed, deficits in language skills, impaired memory and attention deficits .
Workup for Noonan syndrome consists of a patient and family history, physical findings, confirmation of specific abnormalities associated with Noonan syndrome through radiological, laboratory, and genetic tests. A definitive diagnosis of individuals with the Noonan syndrome is achieved by genetic testing. Family history should be elicited for any immediate family members that have mild facial abnormalities and cardiac defects.
Physical findings commonly associated with Noonan syndrome include short stature, congenital heart defects (e.g., pulmonary valve stenosis, cardiac hypertrophy, atrial septal defect), broadened neck or webbed neck, either a protruding chest or pectus excavatum, low-set nipples, undescended testicles, abnormal facial characteristics (e.g., bright blue or green colored iris, wide-spaced eyes, low-set fleshy ears) . Noonan syndrome should be considered in individuals with pulmonary valve stenosis, eye abnormalities (e.g., epicanthal folds, ptosis, ocular hypertelorism), and micrognathia . Individuals with Noonan syndrome often may have either pectus excavatum or pectus carinatum. Scoliosis may also be present.
Occasionally the disorder will be diagnosed prenatally when there is an abnormal maternal serum triple screen, non-invasive prenatal testing, or prenatal ultrasound . Ultrasound abnormalities associated with Noonan syndrome consist of polyhydramnios, cystic hygroma, anatomical cardiac abnormalities, and fetal musculoskeletal anomalies.
Most people with Noonan syndrome have congenital heart disease . The most common cardiac conditions are pulmonary valve stenosis and hypertrophic cardiomyopathy. Tests that can be used to evaluate the heart include echocardiogram , cardiac catheterization (to examine the rate of cardiac blood flow and measure the pressure within the heart), and an electrocardiography to screen for electrical abnormalities or arrhythmias (e.g., left anterior hemiblock, left axis deviation).
Bleeding disorders have been associated with Noonan syndrome. Coagulation studies are used to screen for coagulation factor deficiencies and platelet dysfunction.
Genetic testing permits definitive diagnosis of Noonan syndrome . Affected individuals will have normal chromosome studies. Mutations in the PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, or MEK1 genes are identified in two-thirds of people with Noonan syndrome  . The clinician should keep in mind that not all patients with Noonan syndrome have a detectable alteration in one of these genes and therefore a failure to identify a mutation in one of the aforementioned genes does not exclude the diagnosis of Noonan syndrome.