Noonan Syndrome is a genetic condition that affects many areas of the body. People with Noonan Syndrome often have some of the following issues:
- Distinctive facial features (most obvious in babies and children and more subtle in adults)
- 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)
- Blood clotting (coagulation) defects
- Unusual shape of the chest, such as superior pectus carinatum (protruding chest) or inferior pectus excavatum (sunken chest)
- Low-set nipples
- Undescended testicles in males (cryptorchidism) and possible infertility
- Delayed puberty in males and females
- Special education needs
Not all of these issues will apply to every person with Noonan Syndrome.
RASopathies. At least three conditions are closely related to Noonan Syndrome and have some similar issues. Because of the similarities, together these syndromes are called RASopathies.
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 NSML 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 people with NSML may also develop hearing loss.
A second condition related to Noonan Syndrome is Cardiofaciocutaneous (CFC) Syndrome. People with CFC Syndrome have facial, skeletal, and cardiac features that are similar to those seen in people with Noonan Syndrome. People with CFC 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 CFC Syndrome may also have more severe eating 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 CFC 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 CFC 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.
Genes carry information telling cells in the body how to work. Noonan Syndrome is caused by a change in any one of a group of genes that includes PTPN11, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, and LZTR1. 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 each parent. Cells from people with Noonan Syndrome carry one working copy and one copy that is changed of PTPN11, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, or MAP2K1, or two changed copies of LZTR1. These changes cause the gene to not work right. It is called a variant.
Variants in PTPN11, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, and LZTR1 account for 75–80% of Noonan Syndrome cases. Variants in PTPN11 are found in about 50% of cases, SOS1 in 10–13% of cases, and RAF1, RIT1, and KRAS each in 5% of cases. Variants in BRAF or NRAS are found in only a small number of Noonan Syndrome cases. For the remaining 20–25% of people with the condition who do not have variants 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 variant in PTPN11, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, or LZTR1 from a parent who also has the syndrome. Other people with Noonan Syndrome have a new gene variant 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 variant, people with Noonan Syndrome have a 50% (1 in 2) chance of passing it on to their children.
NSML is caused by specific variants in PTPN11. CFC is caused by variants in KRAS, MAP2K1, or BRAF. Costello Syndrome is caused by variants in HRAS.
A doctor may suspect this diagnosis based on physical exam and/or after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.
Diagnosing this syndrome is usually done by sequencing the PTPN11, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, and LZTR1 genes to find variants (gene changes).
Genetic testing does not always find a variant that is responsible for the syndrome. A person can still have the syndrome even if no variants in these genes are found. There are likely to be more undiscovered genes that play a role in the development of this syndrome.
People with Noonan Syndrome are at a slightly increased risk of developing some types of cancers and blood disorders, including:
- Myeloproliferative disorder (abnormal production of cells in the bone marrow)
- Juvenile myelomonocytic leukemia (cancer of white blood cells in children)
- Neuroblastoma (cancer of the nerves)
- Embryonal rhabdomyosarcoma (cancer of the muscles)
In addition, people with Noonan Syndrome are at a slightly increased risk of developing certain non-cancerous tumors:
- Giant cell lesions (non-cancerous tumor-like growths that most frequently occur in the jaws)
- Granular cell tumors (non-cancerous tumors generally involving the skin or the mucus membranes)
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, although higher than in people who do not have Noonan Syndrome.
Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well.
Other ideas to reduce the risk of cancer include:
- Eat a healthful diet with lots of fruits and vegetables
- Get regular exercise
- Avoid smoking or using tobacco products
- Avoid secondhand smoke
- Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
- Get medical attention for unusual or ongoing symptoms
Parents should find a health care provider 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 get follow-up care if a problem is found in any of these areas.
Because of the risk of a bleeding disorder, people with Noonan Syndrome should avoid taking aspirin or other blood thinners, unless recommended by a health care provider who knows this syndrome well.
Because of the medical concerns related to this syndrome, specialists in the following areas may need to assess a child with Noonan Syndrome:
- Cardiology
- Hematology
- Endocrinology
- Developmental pediatrics
- Surgery
- Occupational or speech therapy
- Audiology
Resources about Noonan Syndrome:
- Noonan Syndrome Foundation (www.teamnoonan.org/)
- Links to Noonan syndrome clinics (www.teamnoonan.org/doctors-and-clinics)
- Noonan Syndrome Association (www.noonansyndrome.org.uk/)
- Genetics Home Reference (ghr.nlm.nih.gov/condition/noonan-syndrome)
- National Organization for Rare Disorders: Noonan Syndrome (rarediseases.org/rare-diseases/noonan-syndrome/)
Other resources:
- Making Sense of Your Genes: A Guide to Genetic Counseling (www.ncbi.nlm.nih.gov/books/NBK115508/)
Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program