Neurofibromatosis Type 1 (NF1)

Neurofibromatosis type 1 (NF1) is a family cancer syndrome associated with a malignant peripheral nerve sheath tumor (MPNST) and an increased risk of other cancers.

What is neurofibromatosis type 1 (NF1)?

Neurofibromatosis type 1 (NF1) is a genetic condition where tumors (mostly benign) grow on skin, nerves, and bones. It is also known as von Recklinghausen disease.

Signs and symptoms of neurofibromatosis type 1

NF1 symptoms can vary from person to person. Some people have mild symptoms, which might keep them from getting diagnosed right away. Symptoms of NF1 include:

• Café-au-lait spots are light brown areas on the skin. Having six or more of these spots, especially if they are larger than 5 mm (about ¼ inch) in children or 15 mm (almost 5/8 inch) after puberty, may mean NF1.
• Neurofibromas are tumors, usually non-cancerous, that grow from nerve cells and are soft bumps in or under the skin. Larger growths that involve many nerves and affect bones, muscles, or other tissues are called plexiform neurofibromas.
• Lisch nodules are tiny bumps on the iris, which is the colored part of the eye. They usually do not affect a person’s vision.
• Optic nerve glioma is a tumor on the optic nerve. The optic nerve connects the eye to the brain.
• Clusters of freckles in unusual places, like the underarm or groin
• Bone problems, such as a curved spine (scoliosis) or curved long bones (such as the legs)
• Learning challenges such as issues with reading or math.
• Larger head size than average
• Shorter height than average

What causes neurofibromatosis type 1 (NF1)?

NF1 is caused by a change (mutation) in a gene called NF1. The NF1 gene, located on chromosome 17, makes a protein called neurofibromin. Neurofibromin is a tumor suppressor protein and helps control cell growth. When NF1 is mutated, it can no longer make normal neurofibromin, which allows tumors to form.

Approximately 50% of NF1 cases are inherited from a parent, while the other 50% of cases arise from spontaneous mutation in the NF1 gene.

How common is neurofibromatosis type 1 (NF1)?

NF1 affects about 1 in every 3,000 people worldwide. This means millions of people around the world are living with NF1.

How is neurofibromatosis type 1 (NF1) diagnosed?

Doctors consider a diagnosis of NF1 if a child has no parental history of NF1 and has two or more of the following:

• Six or more café-au-lait spots if they are larger than 5 mm in children or 15 mm after puberty
• Two or more neurofibromas or one plexiform neurofibroma
• Freckles in the underarm or groin areas
• An optic nerve glioma (also known as an optic pathway glioma)
• Two or more Lisch nodules
• Bone changes

If a child hasa parent with NF1, a diagnosis can be made if that child has one or more of the above criteria. Genetic testing can also be done to confirm the diagnosis.

Does neurofibromatosis type 1 (NF1) increase a person’s cancer risk?

Most NF1 tumors are benign (non-cancerous). However, about 10% of people with NF1 may develop a cancerous tumor called a malignant peripheral nerve sheath tumor (MPNST). This type of tumor grows quickly and can spread to other areas. Early detection and treatment are important.

NF1 is also associated with increased risk of other cancers, such as breast cancer, gastrointestinal tumors (GIST), and sarcomas.

How is neurofibromatosis type 1 (NF1) managed and treated?

Management of NF1

There is no cure for NF1 but regular check-ups and treatments can help manage symptoms and complications.

 Monitoring includes:

• Annual exams with a doctor experienced in NF1
• Yearly eye exams (especially for children)
• Regular blood pressure checks
• Developmental evaluations for children

Treatment

Treatment depends on the type and location of the tumor:

• Watchful waiting: Doctors might monitor tumors that aren’t causing problems.
• Surgery: Tumors that are causing pressure or pain might need to be removed. However, large plexiform neurofibromas can be harder to remove without affecting nearby nerves.
• Medicines: Selumetinib (Koselugo) and mirdametinib (Gomekli) are approved to treat NF1 in children ages 2 years and older with symptomatic plexiform neurofibromas that cannot be surgically removed. They are used to slow the tumor’s growth or shrink it,

Questions to ask your doctor

If you or a family member has NF1, consider asking your doctor:

• What symptoms should I watch for?
• What is my risk of developing malignant tumors or other cancers?
• Are there new treatments or clinical trials I should know about?