This genetic condition affects the normal development of several parts of the body which can include unusual facial features, developmental delays, heart defects, bleeding problems, short stature and other physical problems. In addition, these affected individuals can also develop cancer particularly leukemia. The prevalence of Noonan syndrome is estimated to affect around 1 in 1,000 to 2,500 people.
Causes
Noonan syndrome develops because of a genetic mutation in PTPN11 gene, SOS1 or RAF1 and RIT1 genes. Other genetic causes have also been identified in a small number of cases. These genes are necessary for the production of proteins involved in cell signaling pathway needed for cell division, growth, to carry out specific functions and migration. The genetic mutation causes the resulting protein to be active longer than normal which alters the signaling and disrupts the regulation of the cellular growth and division. This syndrome is inherited in an autosomal dominant pattern meaning a single copy of the defective gene in each cell can cause the condition.
Symptoms
The symptoms can vary greatly among the affected individuals that can range from mild to severe form of the disease. The facial features include wide-set eyes, low-set ears, depression of the nose at the top, small lower jaw, crooked teeth, coarse facial features that can become sharper with age, a large head with a prominent forehead and the skin that can appear to be thin. Most of the children are born with a heart defect which can occur later in life. These can include valve disorders, thickening of the heart muscle, irregular heart rhythm, a hole in the wall that separates the two lower chambers of the heart (ventricular septal defect) or narrowing of the major blood vessels. Additional features can include slow growth, low growth hormone levels causing short stature, deformities of the spine and hearing problems. The abnormalities of the eye include strabismus, nearsightedness, cataracts and rapid movement of the eyeballs. They may also experience excessive bleeding because of clotting defects or from too little platelets in the blood. The genital and kidney conditions can include undescended testicles, delayed puberty and kidney problems among a small number of cases.
Diagnosis
This condition can be prenatally diagnosed with the presence of the excessive amniotic fluid, structural heart difference and other fetal anomalies. In most of the cases, diagnosis is possible with the identification of the associated features and with various specialized tests. Noonan syndrome may be suspected in the case of congenital pulmonary valve stenosis and eye abnormalities. The cardiac tests include electrocardiography, echocardiography and a cardiac catheterization. In addition, blood tests can also detect the potential coagulation factor deficiencies and platelet dysfunction.
Treatment
Early intervention is important for the affected children to help them reach their potential. The congenital heart defects may require medications or surgical intervention based on the severity of the condition. In the case of coagulation factor deficiencies or platelet dysfunction, preventive measures may be necessary to control the abnormal bleeding. Short stature can be treated with growth hormone and additional treatment options include speech therapy, physical therapy and special remedial education.
References
http://www.mayoclinic.org/diseases-conditions/noonan-syndrome/symptoms-causes/dxc-20229210
http://www.nhs.uk/conditions/Noonan-syndrome/Pages/introduction.aspx
https://ghr.nlm.nih.gov/condition/noonan-syndrome#inheritance
https://rarediseases.org/rare-diseases/noonan-syndrome/
