What Is Neurofibromatosis Type 1 (NF1)?

Neurofibromatosis type 1 (NF1) is a genetic condition that affects the skin, nervous system, and other parts of the body. The condition, formerly called Von Recklinghausen disease, causes changes in skin pigmentation and leads to the growth of benign (noncancerous) tumors on nerves, called neurofibromas. These tumors can develop on the skin, in the brain and spinal cord, and throughout the body. NF1 may also affect the eyes, bones, and learning abilities.

The condition is the most common form of neurofibromatosis and occurs in about 1 in 3,000 births worldwide each year. While symptoms can vary widely, the most visible features include light to dark brown skin spots known as café au lait macules, and soft lumps under the skin caused by neurofibromas.

Symptoms of NF1 are usually seen at birth or shortly afterward — almost always by age 10. Which symptoms a person has and the severity of the symptoms can vary from person to person.

Symptoms may include:

• Flat, Light-Brown Spots on the Skin Called café au lait spots, these spots are harmless. They are common in many people, but more than six of them suggests NF1. Café au lait spots are usually present at birth or develop during the first few years of life and stop appearing after childhood.
• Freckles in Skin Folds Small clusters of freckles appear in areas such as the armpits, groin, or under the breasts.
• Neurofibromas These are soft, pea-size or larger lumps under or on the skin. They are noncancerous nerve tumors and may increase in number with age.
• Plexiform Neurofibromas These are larger tumors that grow along nerves or involve bundles of nerves. While they are initially benign, they can sometimes become cancerous over time.

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• Eye Changes Growths on the iris called Lisch nodules can occur, as can tumors along the optic nerve (optic gliomas), which may affect vision.
• Bone Abnormalities These may include curved leg bones, scoliosis (curved spine), larger-than-average head size (macrocephaly), and shorter stature.

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• Neurological Symptoms These can include learning disabilities, developmental delays, attention deficit hyperactivity disorder (ADHD), headaches, and sometimes seizures.
• Other Health Issues High blood pressure, chronic pain, and difficulty moving when tumors press on organs or nerves can all occur in HAE.

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About half of people with NF1 inherit the condition from one of their parents. It can be inherited from a parent in an autosomal dominant pattern, meaning just one altered gene is enough to cause the condition. As a result, there is about a 50 percent chance that a person with NF1 will pass it on to their children.

If NF1 isn’t diagnosed at birth, parents often seek a diagnosis for their children because they notice the café au lait spots, says Roy Strowd, MD, a professor of neurology at Wake Forest University School of Medicine and a codirector of the neurofibromatosis clinic at Atrium Health Wake Forest Baptist in Winston-Salem, North Carolina.

“While NF1 is a genetic condition, we actually use our clinical exam to establish a diagnosis,” says Dr. Strowd. A clinical diagnosis is when a doctor figures out what illness or condition you have on the basis of your symptoms, your medical history, and a physical exam.

“For a formal diagnosis, patients must have at least two of the characteristic diagnostic findings that we can identify on our clinical exam,” says Strowd.

Those findings include:

• Six or more café au lait spots
• Freckling in the armpit or groin
• Two or more neurofibromas or one plexiform neurofibroma
• Two or more Lisch nodules or iris hamartomas (bumps on the iris of the eye)
• Optic pathway glioma
• Curving of the bones of the shin
• An NF1-associated gene variant on genetic testing
• A parent with NF1

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Common Diagnostic Procedures

Diagnostic procedures and tests that are used to diagnose NF1 include:

• Imaging tests, including an MRI, X-ray, or CT scan
• Genetic testing
• An eye exam

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There is no cure for the NF1 condition as a whole, but treatments are available for most of the symptoms a person may have or develop, says Rebecca Brown, MD, PhD, an associate professor at the University of Alabama at Birmingham Department of Neurology and the director of the UAB Neurofibromatosis Clinic.

Medical Care and Monitoring

People with NF1 should have a yearly medical checkup and an annual eye exam to look for changes that may signal new problems.

Targeted Treatments

Mirdametinib (Gomekli) inhibits MEK1/2, which are key mediators in the mitogen-activated protein kinase (MAPK) pathway. Overactivation of the MAPK pathway causes uncontrolled cell growth and tumor formation.

Cancer Treatment

Potential Future Treatments

Surgery

If a tumor is growing, causing symptoms or pain, or there is a concern about cancer, it may be surgically removed.

Physical and Occupational Therapy

Learning and Therapeutic Support

Light Therapy

People with NF1 have a higher risk of complications, including:

• Attention deficit hyperactivity disorder (ADHD)
• Blindness caused by a tumor in an optic nerve (optic nerve glioma)
• Fracture in the leg bones that does not heal well
• Loss of function in nerves that a neurofibroma has put pressure on over the long term
• Tumors of the face and other exposed areas

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• Heart and blood vessel problems, including congenital heart defects, high blood pressure, narrowed kidney arteries, or narrowed brain blood vessels
• Spinal issues, such as a severe form of scoliosis (curved spine)
• Higher risk of certain tumors, including digestive system tumors, hormone-related tumors, and some benign nerve tumors
• Breast cancer risk, which is increased in women with NF1 before age 50

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People with NF1 have a normal life expectancy and fertility for the most part, says Dr. Brown. “The big exception is for people who develop cancer or an aggressive brain tumor. While we cannot predict who will be affected in the future, we can keep close tabs on the health of the whole body for people with NF1 and try to catch and treat any concerning tumors early,” Brown says.

The same goes for skin, heart, and gut health, she adds. “There is a lot to keep track of, but the experts in this field are up to the ‘heaving lifting.’”

Routine checkups with doctors familiar with NF1 — often a neurologist, geneticist, or NF specialty clinic — can detect complications early.

Because symptoms vary widely, some people may go undiagnosed until later in life. Increased awareness and access to genetic testing have improved diagnosis rates in recent decades.

There are some conditions that are more common in people with NF1.

• Hypertension (High Blood Pressure) In NF1, blood vessels can be affected, making high blood pressure more common.
• ADHD Many children with NF1 have changes in brain development that make attention and focus harder.
• Scoliosis NF1 can affect bone growth, which increases the risk of abnormal spine curves.

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• Neurofibromatosis type 1 (NF1) is a genetic condition that causes skin changes, noncancerous tumors on nerves, and, in some cases, learning or bone issues.
• While there is no cure, regular medical checkups and monitoring can help manage symptoms and catch complications such as vision problems, high blood pressure, or tumor growth early.
• New treatments, including targeted drugs like MEK inhibitors, are showing promise in shrinking large tumors and improving quality of life for people with NF1.
• Most people with NF1 have a normal life expectancy, though there is a higher risk of certain cancers, making ongoing care with specialists especially important.