Noonan syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at November 28, 2016
StartDiseasesNoonan syndrome

Noonan syndrome is the result of a genetic mutation that can be inherited or occur spontaneously. The condition can affect various body systems and cause developmental delays. The symptoms of Noonan syndrome are normally apparent at birth.

Contents

Definition & Facts

Noonan syndrome is named after Dr. Jacqueline Noonan, a pediatric cardiologist, who studied children with a particular combination of congenital heart defects and physical characteristics. The condition is more prevalent in males than females. The exact prevalence of the condition is somewhat difficult to determine, but it is believed to occur in approximately 1 in 1,000 to 2,500 births.

The true frequency of the condition may be underreported since the symptoms can vary significantly from person to person. Diagnosis is also complicated by the fact that the symptoms of Noonan syndrome are similar to those of other genetic disorders, including cardiofaciocutaneous syndrome, Turner syndrome, and Costello syndrome.

Symptoms & Complaints

Individuals with Noonan syndrome often have distinctive facial characteristics, including 

Most children born with Noonan syndrome are born normal size, but their growth slows with time resulting in short stature. One of the first signs that an infant may have Noonan syndrome is a buildup of fluid in the hands and feet known as lymphedema. Skeletal defects, including a sunken or protruding check and scoliosis, are also common.

Pulmonary valve stenosis, which is a narrowing of the heart valve controlling blood flow between the heart and lungs, has also been associated with Noonan syndrome. Some patients with the condition develop bleeding disorders that can cause prolonged bleeding and excessive bruising.

Males with the condition often experience delayed puberty and infertility while females tend to experience normal puberty and fertility. Noonan syndrome does not typically affect intelligence, but some children with the condition do have special educational needs as well as hearing problems and vision problems.

Causes

Abnormalities in several different genes can cause Noonan syndrome. A mutation in the PTPN11 gene accounts for roughly half of Noonan syndrome cases. A mutation in the SOS1 gene is responsible for an additional 13 to 15 percent of cases. Other common mutations associated with Noonan syndrome include the KRAS gene, RIT1 gene, RAF1 gene, NRAS gene, RRAS gene, MEK2 gene, and BRAF genes.

Mutations involving the KRAS gene tend to be associated with more severe forms of the disorder. There may be additional genes associated with Noonan syndrome since the cause of the disorder is not identified in about 20 percent of cases.

The genes associated with Noonan syndrome carry instructions that tell the body to make certain proteins vital to tissue formation, cell division, cell differentiation, and cell movement. The mutation may cause the protein to remain continuously active instead of switching on and off. This disrupts the regulation of cell division and growth, which leads to the development of the characteristic features associated with Noonan syndrome. 

Diagnosis & Tests

Certain findings on a prenatal ultrasound may lead a doctor to suspect Noonan syndrome. More often, Noonan syndrome is diagnosed after birth after the doctor observes the distinctive physical characteristics. Since some of the symptoms can be subtle, the condition may not be diagnosed until adolescence or adulthood when short stature and other characteristics are more apparent.

In some cases, molecular genetic testing may be used to confirm the diagnosis. If there is evidence of a heart defect, the child may be referred to a cardiologist for further evaluation and testing. This may include an electrocardiogram and an echocardiogram to assess the electrical activity and physical functioning of the heart.

A cardiac catheterization may help measure the pressure inside of the heart as well as identify possible structural abnormalities. Blood tests may be useful in identifying platelet dysfunction and coagulation factor deficiencies that can cause bleeding disorders.

Treatment & Therapy

Treatment for Noonan syndrome is based on the type and severity of the symptoms. The various health issues and complications associated with the condition are treated the same as they would be among the general population. Most patients with the condition are advised to have periodic heart monitoring by a cardiologist. Medications and surgery may be effective in treating the various heart conditions associated with Noonan syndrome.

Since delayed growth is common with Noonan syndrome, patients with the condition should have their growth monitored on a regular basis. Blood chemistry, bone growth, and hormone levels should also be monitored. If insufficient growth hormone is contributing to delayed growth, hormone therapy may be required.

Infants with the condition often have feeding difficulties that can result in stunted growth and failure to thrive. These children may require supplemental nutrition or other interventions to ensure adequate nutrition.

Patients with a history of excessive bruising should avoid aspirin products and should follow preventative measures recommended by their health care provider when undergoing surgery or dental procedures. Depending on the severity of the bleeding disorders, medications may be required to ensure proper blood clotting.

Regular eye examinations are recommended to identify and address vision problems associated with Noonan syndrome. Children with behavioral or developmental issues caused by the condition may require early interventions and services to help them reach their full potential. This may include speech therapy, remedial education, occupational therapy, and physical therapy

Prevention & Prophylaxis

The genetic mutation that causes Noonan syndrome is autosomal dominant. That means that the child only has to receive one copy of the defective gene to inherit the condition. Approximately half of the children born with Noonan syndrome have an affected parent. An affected parent has a 50 percent chance of passing the gene to their child with each pregnancy.

Individuals with a family history of Noonan syndrome may want to consult a genetic counselor so that they can make an informed decision about having children. There is no way to prevent Noonan syndrome in cases where the genetic mutation occurs spontaneously. When detected early, comprehensive care can help reduce the risk of heart complications and other complications.