Neurofibromatosis Type 1

Approved by the Cancer.Net Editorial Board , 06/2023

What is neurofibromatosis type 1?

Neurofibromatosis type 1 (NF1) is a hereditary condition commonly associated with multiple café-au-lait spots on the skin. Café-au-lait spots are light brown in color, like the color of “coffee with milk.” About 10% to 25% of the general population has café-au-lait spots; NF1 is suspected when a person has 6 or more.

People affected by NF1 also tend to develop varying numbers of neurofibromas, meaning benign (noncancerous) tumors on the covering of the nerves. Neurofibromas are often seen as raised bumps on the skin and can occur anywhere on the body. While these skin changes do not have serious medical consequences, they can affect a person’s appearance. Plexiform neurofibromas, which form under the skin or deeper in the body, are also benign tumors. However, these can grow quite large and can cause significant medical problems, affecting the structure of nearby bone, skin, and muscle.

Other benign and cancerous tumors that can occur from NF1 include:

  • Eye tumors, including Lisch nodules, which grow on the iris of the eye, and optic tumors called optic nerve glioma or optic pathway glioma

  • Brain tumors and spinal cord tumors

  • Malignant peripheral nerve sheath tumors (MPNST), also called neurofibrosarcoma, that is sarcoma that grows from the cells around nerve ending

  • Other sarcomas , including muscle tumors

  • Breast cancer

  • Adrenal gland tumors called pheochromocytoma

Recent research has also associated NF1 with these cancers:

  • Melanoma

  • Neuroendocrine tumors

  • Ovarian cancer

  • Prostate cancer

Some other features of NF1 include:

  • High blood pressure

  • Learning disabilities, which can occur in about 50% of children with NF1

  • Childhood leukemia

  • Bone changes

  • Scoliosis, meaning curving of the spine

  • Short stature (height)

The number of features present and how severe the symptoms are can vary among people with NF1, even within the same family. Sometimes NF1 is “segmental,” meaning that it affects only 1 portion of the body, such as 1 leg or 1 arm. Research continues into the features of NF1, including the risk of cancer.

Statistics adapted from the Children's Tumor Foundation (Accessed June 2023).

What causes NF1?

NF1 is a genetic condition. This means that the cancer risk and other features of NF1 can be passed from generation to generation in a family. The gene commonly associated with NF1 is also called NF1 . The gene is noted in italics to help distinguish the gene from the condition. A change, also called a mutation or alteration, in the NF1 gene gives a person an increased risk of developing the various symptoms of NF1, including cancerous and benign tumors. Most people with NF1 have a mutation in the NF1 gene. It is now believed that mutations in other genes may also produce multiple nerve tumors.

In particular, a different tumor suppressor gene called INI 1 may cause multiple schwannomas, a type of tumor of the nervous system, on nerves in some people. This condition is called schwannomatosis, and this is a similar but different disease from NF1 since the main identifying feature of NF1 is neurofibroma rather than schwannomas. (Learn more about schwannomatosis on a separate, independent website.) Both are tumors that grow on nerves, but they have different causes. Research is ongoing to learn more about NF1 and other diseases causing nerve tumors.

How is NF1 inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. NF1 follows an autosomal dominant inheritance pattern, in which a mutation happens in only 1 copy of the gene. This means that a parent with a NF1 mutation may pass along a copy of their normal gene or a copy of the changed gene. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A sibling or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. Eggs are removed from the ovaries and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over 2 decades and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is NF1?

NF1 is among the most common genetic conditions. It is estimated that as many as 1 in 3,000 people worldwide have an NF1 mutation. About 30% to 50% of people affected by NF1 do not have any family history of the condition. They have a de novo (new) mutation in the NF1 gene. However, the children of anyone with NF1 have a higher risk of inheriting the condition.

Statistics adapted from the National Institute of Neurologic Disorders and Stroke (Accessed June 2023).

How is NF1 diagnosed?

NF1 is diagnosed when a person meets the official diagnostic criteria for NF1 that was developed at a National Institutes of Health Consensus Conference in 1987. Based on these criteria, a person who has at least 2 of the following features is considered to have NF1:

  • 6 or more café-au-lait spots. These spots must be more than 5 millimeters (mm) in diameter in young children and more than 15 mm in diameter after puberty.

  • 2 or more neurofibromas or 1 plexiform neurofibroma

  • Freckling around the armpits or groin

  • Optic glioma

  • 2 or more Lisch nodules

  • Specific bone changes, including sphenoid dysplasia, which is an abnormality of 1 of the bones forming the skull, or thinning of the long bones

  • A parent, sibling, or child with NF1

If a person has a family history of NF1, they are suspected of having NF1 if they have any features of the condition. Genetic testing for mutations in the NF1 gene is available for people diagnosed with NF1.

What are the estimated cancer risks associated with NF1?

Most tumors from NF1 are benign. In general, the lifetime risk of cancer developing in a person with NF1 is estimated to be low. When cancer does occur, it generally happens when a benign neurofibroma turns into a cancerous form called MPNST, which grows much faster, invades nearby structures, and sometimes metastasizes (spreads) to other areas of the body. MPNST will develop in about 10% of people with NF1. It is important to talk to your doctor who specializes in NF1 about other specific cancer risks from NF1, including a higher risk of breast cancer for women with NF1 under age 50.

Statistics adapted from the Children's Tumor Foundation (Accessed June 2023).

What are the screening options for NF1?

Suggested screenings for people affected by NF1 or at risk for NF1 include:

  • Yearly examination by a doctor who is experienced with NF1

  • Yearly eye examinations, beginning in childhood. This may become less frequent in adulthood.

  • Yearly blood pressure monitoring

  • Developmental and educational evaluations in childhood, as needed

  • Other evaluations, such as imaging scans, like a computed tomograpy (CT or CAT) scan or magnetic resonance imaging (MRI) , as needed for symptoms

Screening recommendations may change over time as new technologies are developed and more is learned about NF1. It is important to talk with your health care team about appropriate screening tests, as well as what new symptoms you should report to them right away. In some areas, comprehensive NF1 clinics may be available to help with coordination of your medical care.

Learn more about what to expect when having common tests, procedures, and scans .

What are ways of treating tumors related to NF1?

The usual treatment approach for any tumors associated with NF1 is to watch the person closely for signs of tumor growth or whether the person is having such symptoms as pain or weakness. This is called watchful waiting, watch and wait, or active surveillance.

If symptoms develop over time, then surgery may be done to remove the tumor(s). It is usually possible to remove a tumor growing on or from nerves, and to preserve the nerve involved, unless it is a plexiform tumor. Plexiform tumors are more spread out and often get into the nerve, which makes it harder to remove the tumor without hurting the nerve. A cancerous tumor may be treated with cancer medications such as chemotherapy , radiation therapy , or a combination of treatments. Clinical trials , meaning research studies, for neurofibromatosis are ongoing and currently focus on targeted therapy drugs that affect the ras signaling pathway inside the tumor cell. Ras communicates signals from outside the cell to the nucleus of the cell. Problems in the ras pathway are common in tumors linked to NF1.

Questions to ask the health care team

If you are concerned about your risk of cancerous or benign tumors from NF1, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing these types of tumors or cancer?

  • What can I do to reduce my risk?

  • What are my options for screening?

  • What symptoms should I watch for? How soon should I report those to you?

If you are concerned about your family history and think you or other family members may have an NF1 mutation, consider asking the following questions:

  • Does my family history increase my risk of developing cancer?

  • Will you refer me to a genetic counselor or other genetics specialist?

  • Should I consider genetic testing ?