Noonan Syndrome

What is Noonan syndrome?

Noonan syndrome is a genetic condition that affects many areas of the body. People with Noonan syndrome often have some of the following features:

Facial features (most obvious in babies and children and more subtle in adults):

A deep groove in the philtrum (the area between the nose and mouth)

Widely-spaced eyes that are vivid blue or blue-green in color. The eyes may have epicanthal folds (skin folds of the upper eyelid that partially cover the inner corners of the eyes) and thick or droopy eyelids

Low-set ears that are rotated backward or are unusually fleshy

Broad neck or webbed neck

Short stature (height for age less than the third percentile)

Lymphedema (puffiness) in the hands and feet in newborns

Feeding problems in newborns and infants

Abnormal heart, present at birth (congenital heart defects), such as the following:

Pulmonary valve stenosis (heart valve disorder in which blood does not flow through the heart properly)

Hypertrophic cardiomyopathy (thickening of the heart muscle)

Atrial septal defect (abnormal hole between the two sides of the heart)

Doctors do not know the exact risk of developing tumors or cancer for people with Noonan syndrome. The overall risk appears to be very low. At this time there are no standard cancer screening recommendations for people with Noonan syndrome.

What are other conditions related to Noonan syndrome?

At least three conditions are closely related to Noonan syndrome that have some similar features.

One condition is known as Noonan syndrome with multiple lentigines (NSML), previously called LEOPARD syndrome (Lentigines, ECG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, Deafness). People with Noonan syndrome with multiple lentigines share many of the same features seen in people with Noonan syndrome, but typically have more skin findings. These include café au lait patches (coffee-colored, flat birthmarks) and lentigines (small colored spots on the skin with clearly-defined edges). Some patients with Noonan syndrome with multiple lentigines may also develop hearing loss.

A second condition related to Noonan syndrome is cardiofaciocutaneous (CFC) syndrome. People with cardiofaciocutaneous syndrome have facial, skeletal and cardiac features that are similar to those seen in people with Noonan syndrome. People with cardiofaciocutaneous syndrome, however, have more distinct facial features that are sometimes called “coarse.” These features may include sparse eyebrows and eyelashes, and follicular hyperkeratosis (white bumps on the skin). People with cardiofaciocutaneous syndrome may also have more severe feeding problems than people with Noonan syndrome do. These problems include gastroesophageal reflux (severe heartburn), aspiration (inhaling food particles), vomiting and oral aversion (unwillingness to put things into the mouth). Most people with cardiofaciocutaneous syndrome have intellectual disability.

A third condition related to Noonan syndrome is Costello syndrome. People with Costello syndrome can share features seen in Noonan syndrome and cardiofaciocutaneous syndrome. In addition, people with Costello syndrome can have more problems in the brain. The cancer risk is also higher in people with Costello syndrome, estimated to be 15% during a person’s lifetime.

What causes Noonan syndrome?

Genes carry information telling cells within the body how to function. Noonan syndrome is caused by a change in any one of a group of genes that includes PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF and MAP2K1. These genes are needed for growth and development.

Most people without Noonan syndrome carry two working copies of each these genes in their cells. One copy of each gene is inherited from the mother and one copy of each gene is inherited from the father. Cells from people with Noonan syndrome carry two working copies of each of these genes except one. For that one gene, the person’s cells carry one working copy and one copy that is changed. This change causes the gene to not work properly. It is called a mutation.

Mutations in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF and MAP2K1 account for 70–75% of Noonan syndrome cases. Mutations in PTPN11 are found in about 50% of cases, SOS1 in 10–15% of cases, and RAF1 and KRAS each in 5% of cases. Mutations in BRAF or NRAS are found in only a small number of Noonan syndrome cases. For the remaining 25–30% of people with the condition who do not have mutations in any of these genes, doctors do not yet know what other genes are related to Noonan syndrome.

Some children with Noonan syndrome inherit a gene mutation in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF and MAP2K1 from a parent who also has the syndrome. Other people with Noonan syndrome have a new gene mutation that did not come from a parent. These children have no history of the syndrome in their families. In these cases, the change either happened in an egg or sperm cell when the child was formed or in one of the child’s cells during pregnancy. These children are the first in their families to have Noonan syndrome.

No matter how they acquired the gene mutation, people with Noonan syndrome have a 50% (1 in 2) chance of passing it on to their children.

How is genetic testing for Noonan syndrome done?

The doctor may suspect Noonan syndrome after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about a person’s health and the health of other family members. If Noonan syndrome is suspected in a child or other family members, the doctor or genetic counselor will likely recommend genetic testing of one or more of the genes that are associated with the syndrome (PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF or MAP2K1).

Diagnostic genetic testing

If the doctor or genetic counselor suspects that a person has Noonan syndrome, diagnostic testing may take place as follows:

A blood sample is collected.

DNA is isolated from the cells in the sample. A person’s genes are made of DNA.

Both copies of the person’s genes are checked for possible changes. A genetic specialist compares the two copies of the patient’s genes to normal copies of the genes. If there are differences, the specialist decides if they might cause a certain condition such as Noonan syndrome.

If mutations in the tested gene or genes are found, the genetic counselor will work with the family in the following ways:

To help the family understand Noonan syndrome

To find out if other family members should consider testing

To help with decisions about prenatal genetic testing

It is important to remember that genetic testing does not always find a mutation in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF or MAP2K1 for all people with Noonan syndrome. A person can still have Noonan syndrome even if no mutations in these genes are found. There are likely to be more, undiscovered genes that play a role in the development of Noonan syndrome.

Prenatal genetic testing

Parents may undergo prenatal testing to find out if the pregnancy is affected with a known family mutation in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF or MAP2K1. Testing may take place either before pregnancy occurs or during pregnancy.

People considering prenatal testing should work with a genetic counselor to review the pros and cons of the testing. The genetic counselor can also help parents consider how they wish to handle the results of the testing.

Testing that occurs before pregnancy — Testing that happens before pregnancy is called preimplantation genetic diagnosis (PGD). This special type of genetic testing is done along with in vitro fertilization (IVF). PGD offers a way to test embryos for a known mutation in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF or MAP2K1 before placing them into the uterus.

Testing that occurs during pregnancy — Testing can be used to see if a pregnancy is affected with a known mutation in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF or MAP2K1. A doctor gathers cells from the pregnancy in one of two ways:

Chorionic villus sampling (CVS) — during the first trimester (first three months)

Amniocentesis — during the second trimester or later (last six months)

Collected tissue can be checked for the presence of a known mutation in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF or MAP2K1 that has already been identified in the family.

Both of these tests carry minor risks and should be discussed with an experienced doctor or genetic counselor.

Special concerns

Genetic testing for Noonan syndrome is a complex process. Those thinking about testing should take time to consider the benefits and risks. They should discuss the process with a genetic counselor before testing is done. If they choose testing, they should review the test results with the doctor or genetic counselor to be sure they understand the meaning of the results.

Sometimes children or adults with Noonan syndrome can feel sad, anxious or angry. Parents who pass on a mutation in PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF or MAP2K1 to one or more of their children can feel guilty. Some people with a mutation in one of these genes could have trouble getting disability coverage, life insurance or long-term care insurance in some states. Read more about genetic discrimination.

Are there other special health care needs for children with Noonan syndrome?

Parents should seek out a doctor with experience managing patients with Noonan syndrome for their child. There are clinics throughout the country that specialize in taking care of people with Noonan syndrome. For more information, please see the “Resources” section below.

People with Noonan syndrome should have an initial evaluation of growth and development, heart, eyes, kidneys, hearing, blood and skeleton. Patients should seek follow up care if a problem is found in any of these areas.

People of any age with Noonan syndrome have a slightly higher risk of cancer. They should monitor their health and adopt healthful habits throughout life. It is important to continue to have regular physical checkups and screenings. That way, any cancer can be found early at the most treatable stage. At this time there are no standard cancer screening recommendations for people with Noonan syndrome.

Because of the risk of a bleeding disorder, people with Noonan syndrome should avoid taking aspirin or other blood thinners unless recommended by a doctor who knows this syndrome well.

Other ideas to reduce the risk of cancer include the following:

Eat a healthful diet with lots of fruits and vegetables

Get regular exercise

Avoid smoking or using tobacco products

Avoid secondhand smoke

People with Noonan syndrome should watch closely for general signs or symptoms that could signal cancer:

Additional Resources

The St. Jude Web site is designed for educational purposes only and is not engaged in rendering medical advice or professional services. The information provided through this site should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, you should consult your health care provider.