Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that can be passed down from parents to their children (inherited). People with NF1 have a higher risk of developing certain kinds of tumors. These tumors are usually non-cancerous (benign) but may sometimes be cancerous (malignant).

NF1 can affect many areas of the body. The severity of the condition and the body areas affected can vary.

Cancer risk with neurofibromatosis type 1

Neurofibromas and malignant peripheral nerve sheath tumors

Nearly all people with NF1 develop non-cancerous (benign) cutaneous (on the skin) neurofibromas. Cutaneous neurofibromas may look like bumps under the skin. They usually start to appear in late childhood and teenage years. They can continue to develop throughout life. Many women with NF1 experience a rapid increase in the number and size of cutaneous neurofibromas during pregnancy. These tumors are not cancerous, but may cause itching, occasional pain, and may alter a person’s physical appearance (disfigurement).

Other neurofibromas can grow in childhood and are called subcutaneous (under the skin) or plexiform neurofibromas. While these neurofibromas are not cancerous, they can become large. They may cause pain, nerve damage, or disfigurement.

Plexiform neurofibromas are usually present in young childhood. These tumors can cause pain, push on nearby organs, may affect movement, and alter a child’s appearance (disfigurement). They may first appear either under the skin or they could be deeper inside the body and seen on an imaging exam. These tumors occur in 30–50% of patients with NF1.

A plexiform neurofibroma has a small chance of becoming a cancer called a malignant peripheral nerve sheath tumor (MPNST) during adolescence and adulthood.

About 10% (1 in 10) of people with NF1 will develop an MPNST near a neurofibroma that is already present. It is easier to treat these tumors if they are diagnosed early.

Central nervous system tumors

The 2 most common central nervous system tumors in people with NF1 are optic gliomas and brain tumors. Optic gliomas may form on the optic nerve. This nerve connects the eye to the brain. About 20% (2 in 10) of children with NF1 develop optic gliomas, which usually start in childhood. Often, these tumors do not cause any symptoms, even into adulthood. Children with NF1 should be followed closely by an eye doctor in early childhood to monitor their vision closely.

Tumors may also form in other parts of the brain. About 3% of people with NF1 develop brain tumors (such as gliomas). Most often, these tumors do not cause symptoms and do not need any treatment, but patients with these tumors should be watched closely by a neuro-oncologist. Though less common, aggressive gliomas can develop in people with NF1.

Breast cancer

Women with NF1 who are under age 50 have a higher risk of developing breast cancer than women without NF1. After age 50, the risk is the same for women with and without NF1.

Other cancers

People with NF1 have a higher risk of developing certain other cancers than those without the condition. But the overall risk is still very low. These cancers include:

• Adrenal gland tumors (pheochromocytomas): The adrenal glands are located on top of each kidney. They produce important hormones.
• Leukemia: A type of blood cancer
• Gastrointestinal stromal tumors: tumors in the digestive tract

Other health problems with neurofibromatosis type 1

NF1 can affect many areas of the body. Not all patients will have all of the following, even patients within the same family.

Symptoms of neurofibromatosis type 1

Symptoms of NF1 vary from person to person even within a family. Some symptoms of NF1 are:

• Brown spots on the skin (known as café-au-lait macules)
• Freckles on parts of the skin not normally exposed to sunlight (groin, underarms, under breasts)
• Larger than normal head size
• Small growths in the colored part of the eye (Lisch nodules)
• Benign tumors along the nerves (neurofibromas)
• Tumors in the eye called optic pathway gliomas

People with NF1 should watch closely for general symptoms that could signal a tumor, such as:

• Unexplained weight loss
• Loss of appetite
• Pain in the abdomen
• Blood in the stool or changes in bowel habits
• Aches, pains, lumps, or swelling that cannot be explained
• Headaches or changes in vision or nerve function that do not go away

It is important to seek medical help if anything unusual appears.

Causes of neurofibromatosis type 1

Neurofibromatosis type 1(NF1) is caused by changes in the NF1gene that make it not work correctly. The NF1 gene carries information that helps control how and when cells grow, divide, and die.

How neurofibromatosis type 1 is inherited

Children without this disorder carry 2 normal copies of the NF1 gene in their cells. One copy is inherited from the child’s mother, and the other comes from the child’s father.

Children who do have neurofibromatosis type 1 inherit 1 normal copy of the NF1 gene and 1 copy that is changed (mutated). This NF1 mutation makes the gene not work correctly. As a result, it is harder for cells to control their growth and functions.

About 50% (1 in 2) of children with neurofibromatosis type 1 inherit the NF1 gene mutation from a parent who also has this disorder. The other 50% (1 in 2) of children with this disorder have a new NF1 mutation that did not come from a parent. These children have no history of this disorder in their family. In such cases, an NF1 gene mutation happened either in:

• An ovum (egg) or sperm that formed the child
• 1 of the child’s cells before they were born

These children are the first in their families to have neurofibromatosis type 1.

Some children with a clinical diagnosis of NF1 may not have a mutation in NF1 in their blood cells, but they could be a “mosaic” of NF1. “Mosaic” means a mixture.

Mosaic neurofibromatosis 1

A child with mosaic neurofibromatosis type 1 inherits 2 normal copies of the NF1 gene. One copy is from the mother. The other copy is from the father. But early in development, before the person is born, 1 copy of the NF1 gene becomes mutated (changed) within 1 cell of the developing baby. That cell will keep growing and dividing, making many more cells like it in the baby’s body. All the cells that grow from that early cell have the mutated copy of the NF1 gene. Other cells that did not grow from the 1 mutated cell will have 2 normal copies of the NF2 gene. That is why it is called mosaic NF1; the child’s body is a mixture of normal cells and mutated cells.

With mosaic neurofibromatosis type 1, it is hard to know which cells have the NF1 mutation. In this case, it is not possible to predict the exact risk of passing the NF1 mutation on to future children. The risk is up to 50% (1 in 2) chance of passing the NF1 mutation onto each child.

Children with mosaic neurofibromatosis type 1 generally only have features of the condition in the areas of the body that contain the NF1 mutation.

Diagnosis of neurofibromatosis type 1

Health history

A health care provider may suspect that your child has NF1 after studying their medical and family cancer history.

This information helps the health care provider and the genetic counselor know if:

• There are more tumors than normal in your family
• These tumors happened at a younger age than expected
• The types of tumors are those seen with NF1
• There are family members who have clinical signs of NF1

Your doctor or genetic counselor may recommend NF1 genetic testing if they suspect NF1.

Learn more about types of genetic tests. 

Genetic testing for NF1

A blood sample is sent to a genetic testing lab. The lab runs a special type of genetic test, called next-generation sequencing, that looks for changes in the NF1 gene.

If your child has an NF1 mutation, a genetic counselor will work with your family to:

• Find out if other family members should consider testing for an NF1 mutation
• Help your family understand the increased cancer risk from NF1
• Give you information to help with your decisions about prenatal genetic testing

Genetic testing can detect a mutated NF1 gene in about 90–95% of people with a clinical diagnosis of NF1.

There may be other genes or types of mutations causing this condition that doctors do not yet know about. So, a person can still have NF1 even if no NF1 mutation is found.

People who are mosaic NF1 may not have a mutation in NF1 in their blood cells, but they could be a mosaic NF1. They could have mutated cells in another part of their body.

Genetic testing before or during pregnancy

Parents may choose to do prenatal testing to find out if a pregnancy is affected with a known NF1 mutation.

You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known NF1 mutation before a doctor places an embryo into the uterus.

Testing during pregnancy can help doctors see if a pregnancy has a known NF1 mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:

• Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
• Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for the NF1 mutation. Both tests carry minor risks. Discuss risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

Sometimes, children or adults with NF1 feel sad, anxious, or angry after getting their test results. Parents may feel guilty if they pass the NF1 gene mutation to 1 or more of their children. People with the NF1 gene mutation may also have trouble getting disability or life insurance.

Read more about genetic discrimination.

Diagnosis of neurofibromatosis type 1 without genetic testing

It is possible to get a clinical diagnosis of NF1 without genetic testing. A person with 2 or more features can be diagnosed with NF1. These features are:

• 6 or more café-au-lait spots that measure specific widths in children and adults
• 2 or more neurofibromas or a thick, irregular neurofibroma that affects multiple nerves (known as a plexiform neurofibroma)
• Freckles in the armpits or the groin area
• An optic glioma tumor, which grows in the nerves that carry messages from the eye to the brain
• Two or more Lisch nodules: small growths in the colored part (iris) of the eye
• Bone in the skull that has not formed as normal
• Thinning of the long bones in the body
• A first-degree relative (parent, sibling, child) diagnosed with NF1

If a person has a negative genetic test but still has 2 or more of these features, they can still be diagnosed with NF1.

Monitoring and follow-up care for neurofibromatosis type 1

Monitoring and follow-up care for NF1 depend on how severe the disease is, the location of any tumors that may arise, and a person’s overall health.

Care may involve managing symptoms with medicines and surgery to remove any cancerous tissues or tumors. Care may also include other treatments such as chemotherapy to fight any cancers that may develop. Targeted medications known as MEK-inhibitors can act on specific types of NF1. This is a new way of treating many of these tumors with fewer side effects than chemotherapy.

Radiation treatment for NF1 patients should be avoided if possible.

Because NF1 is a complex condition, parents should discuss screening options for their child with an experienced doctor who knows this condition well. The goal of screening is to find and treat tumors early. Doing so allows the best outcome for patients. There are clinics throughout the country that specialize in taking care of people with NF1.

It is also important that parents also work with a genetic counselor to find experienced doctors for their child. To find a genetics counselor in your area, visit the Personalized Care for Your Genetic Health webpage.

Cancer screenings for NF1 

Although most of the tumors related to NF1 are not cancerous, people with NF1 should be monitored for development of these tumors. Some non-cancerous tumors cause problems. Vision loss can occur from optic pathway gliomas. Neurofibromas may cause nerve damage. It is important to carefully monitor neurofibromas for signs they are becoming cancerous. Early screening and detection allow the best outcome for patients.

The following lifelong screenings are recommended for children with NF1:

• Yearly physical exams that include blood pressure monitoring by a doctor who knows this condition well
• Yearly vision screening by an ophthalmologist (eye specialist) in early childhood, which can become less frequent as the child gets older
• Regular assessments of development and school progress, as suggested by your child’s doctor
• Regular monitoring of any abnormal problems of the central nervous system, skeletal system, or heart and blood vessels, as suggested by a specialist in one of these areas
• Baseline MRI of the whole body when transitioning to adult care

As a child moves into adulthood, they may need more screenings for breast cancer and signs of a malignant peripheral nerve sheath tumor.

These recommendations may change over time as doctors learn more about NF1.

Living with neurofibromatosis type 1

People of any age with NF1 have a higher risk of cancer than people without NF1. They should monitor their health and adopt healthy habits throughout life.

It is important to continue to have regular physical check-ups and screenings. That way, any cancer can be found early and at the most treatable stage.

Maintain a healthy lifestyle 

Habits that will help you maintain a healthy lifestyle include:

• Eat a healthy diet with lots of fruit and vegetables.
• Get regular exercise.
• Avoid excess sun exposure. Always wear a hat, protective clothing, and sunscreen (SPF 30 or higher) when out in the sun.
• Avoid unnecessary radiation exposure.
• Avoid smoking or the use of tobacco products.
• Avoid being around secondhand smoke.
• Avoid excessive alcohol use.

Neurofibromatosis type 1 care at St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve the care and treatment for patients who are affected by these conditions. Learn more about the Division of Cancer Predisposition at St. Jude.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

• A complete health history
• A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
• Physical exams to check for genetic disease
• Confidential genetic counseling and testing
• Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
• Recommended cancer treatments and ways to reduce cancer risk
• Genetic testing for immediate (1st degree) relatives

NF1 increases your child’s risk for tumors and, less commonly, certain cancers. 

Related clinical trials  

St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancers associated with NF1. 

Learn more

If you have questions about the Genetic Predisposition Clinic and care for NF1, email our team at GPTeam@stjude.org.

Resources outside St. Jude