NF1: plexiform neurofibromas and other complications

Neurofibromatosis is a group of rare genetic disorders that affect the skin and nervous system. Neurofibromatosis type 1 (NF1) is the most common type.

The underlying causes are changes (mutations) that affect the NF1 gene, which provides the body with instructions for making a protein called neurofibromin. Neurofibromin is a tumor suppressor protein, or a protein that regulates the growth of cells. When a person has NF1, this protein does not function normally, and cells grow in uncontrolled ways. The mutations that cause NF1 can be inherited or occur sporadically.

Symptoms of NF1 often begin in a person’s childhood and can include light brown patches on the skin called cafe-au-lait macules (CALMs) and freckling in unusual spots, such as the underarms or groin. Additionally, learning difficulties, developmental delays, and attention deficit hyperactivity disorder (ADHD) are common among children with NF1.

Another characteristic symptom of NF1 are neurofibromas. Neurofibromas are benign (noncancerous) tumors that grow on nerve fibers. These tumors appear as soft, pea-sized lumps that form on or underneath the skin.

Plexiform neurofibromas

Larger tumors called plexiform neurofibromas are also common, occurring in roughly half of people with NF1.

Plexiform neurofibromas can cause nerves to become thickened and misshaped, affecting how nerves function. While plexiform neurofibromas do not grow in the brain or spinal cord, they can occur almost anywhere else in the body, with common locations being the face, eye socket, neck, limbs, abdomen, and back. Plexiform neurofibromas that occur beneath the skin are sometimes described as bulging and looking or feeling like a “bag of worms.”

Larger plexiform neurofibromas can put pressure on surrounding tissues and structures, which can cause significant health problems and complications depending on the size and location. For example, a plexiform neurofibroma that occurs near the eye can cause vision loss, disfigurement, and affect the functioning of the brain.

Complications of NF1

Other serious complications and health risks associated with NF1 include:

• Tumors on the optic nerve (the nerve that connects the eyeball to the brain) which can result in vision loss
• Vascular disorders, including high blood pressure, narrowing of the blood vessels that supply the brain, and hardening of the arteries that supply the kidneys
• Scoliosis, or curvature of the spinal column
• Problems with growth and development, such as short stature and/or enlarged head

While neurofibromas are benign, people with NF1 are at risk of developing a cancer called malignant peripheral nerve sheath tumor (MPNST).

People with NF1 are also at a higher risk of multiple types of other benign or cancerous tumors, including:

• Breast cancer
• Leukemias
• Gastrointestinal tumors
• Adrenal gland tumors
• Gliomas (tumors that occur in the brain and spinal cord)

Treatment for NF1

There is no cure for NF1, and the main goals of treatment are to address symptoms and prevent complications. Surgery may be used to remove tumors, but is often not possible with plexiform neurofibromas. Smaller skin neurofibromas may be treated with laser or electrocautery therapies.

Recent years have seen the approval of several medications that either stop/slow tumor growth or reduce the size/number of tumors.

For NF1 that becomes cancerous, treatment may involve cancer therapies like chemotherapy and radiation therapy.

Supportive therapies are also important. These are therapies that help address specific symptoms, such as therapies to help with vision loss, hearing loss, ADHD, mobility issues, or other problems that occur as a result of the condition.

It should be emphasized that NF1 varies significantly from person to person. While everyone will need monitoring to check for new symptoms or complications, treatment is highly individualized, based on a person’s age, symptoms, health, and other factors.

If you or a loved one has been diagnosed with NF1 or another form of neurofibromatosis, your best source of information about symptoms, diagnosis, complications, and treatment will be a healthcare provider.