What Is Neurofibromatosis?

Neurofibromatosis (NF) is a group of genetic disorders that can affect the body in many ways, including causing the growth of tumors on nerve tissue.

There are four types of neurofibromatosis:

• Neurofibromatosis 1 (NF1)
• Neurofibromatosis 2 (NF2)
• Schwannomatosis
• Legius syndrome

Each type of neurofibromatosis is caused by a unique, separate genetic change (mutation). Children who have one type of neurofibromatosis are not at increased risk of getting another type.

Children can inherit the genetic change from one of their parents. However, half of children with NF1 or NF2 do not have a family history of the condition. Anyone who has NF1 has a 50% chance of passing the condition on to each of their children.

Neurofibromatosis 1

Neurofibromatosis 1 is the most common type of neurofibromatosis, affecting 1 in 3,000 people. NF1 is characterized by:

• Tumors
• Changes in skin pigment
• Bone abnormalities
• Learning disabilities

A genetic change on chromosome 17 causes neurofibromatosis 1.

NF1 can affect every person differently, even among family members who have the condition. Symptoms can worsen over time or stay the same. About two-thirds of people with NF1 have mild to moderate symptoms during their lives. The other third will have more severe complications at some time during their life.

Neurofibromatosis 1 Tumors

The most common feature of NF1 seen in young children is café-au-lait spots. These are flat, oval-shaped spots on the skin that are about 2-3 shades darker than the child’s usual skin color.

Another frequent feature of NF1 is the appearance of certain types of tumors. One example is dermal (skin) neurofibromas, small bumps that can occur anywhere on the skin. They are benign growths (do not become cancerous). They usually begin in teenage years and people develop more of them over time. Some people can have hundreds to thousands of dermal neurofibromas by the time they are older adults. Dermal neurofibromas are not cancerous. They don’t need to be removed unless they are causing pain or discomfort.

Plexiform neurofibromas (PNs) are a larger type of neurofibroma that usually begin in childhood. They usually appear as a soft mass under the skin. Some are inside the body and not visible to the human eye. They begin inside a network of larger nerves coming off the spinal cord and can extend into healthy tissues. PNs can become large and press on structures anywhere on the body, which can be painful. These tumors are often difficult to remove with surgery. There is a small chance that cancer can develop within a plexiform neurofibroma over time.

Other Symptoms of Neurofibromatosis 1

Children with neurofibromatosis 1 can experience additional symptoms, such as:

• Freckles in the armpits or groin
• Dome-shaped nodules on the iris (colored part) of the eye; these are called Lisch nodules
• Mild difficulties with motor coordination. Children with NF1 tend to reach motor milestones (such as crawling and walking) a bit later than other children.
• Learning disabilities. About 60% of children with neurofibromatosis 1 will have some type of learning disability or attention deficit hyperactivity disorder (ADHD).
• Migraine headaches
• Vascular problems, which can cause high blood pressure and other concerns
• Skeletal and bone abnormalities:
  • Short stature. People with NF1 tend to be a little shorter than other family members. They also tend to have larger heads.
  • Scoliosis. About 15-20% of children with NF1 can develop scoliosis (sideways curvature of the spine), sometimes early in childhood. This condition can worsen over time and may require surgery.
  • Tibial dysplasia. About 3% of children with NF1 develop this condition, where the shin bone bows out and can fracture easily.

NF1 Diagnosis

NF1 Treatment

Scientists have not discovered a cure for neurofibromatosis 1 yet, but they are developing more effective treatments. One example is a new way to treat inoperable plexiform neurofibromas that uses a drug called selumetinib (also known as Koselugo). This drug can partially shrink plexiform neurofibromas in about 70% of patients who are treated with it.

Other treatment for NF1 focuses on managing symptoms. For example:

• If the child has migraines, a pediatric neurologist will provide a complete evaluation and may prescribe medication.
• If the child has bone or skeletal abnormalities, a pediatric orthopaedic specialist can provide care. Bracing or surgery may be recommended for scoliosis. A leg brace may be recommended for tibial dysplasia.
• If the child is having learning issues or behavior problems at school, the care team may recommend a full neuropsychological exam. School-based services can help the child thrive.
• If the child is experiencing emotional distress because of their condition, mental health counseling may help.

Children with neurofibromatosis 1 should receive care from doctors who specialize in neurofibromatosis care if possible. Geneticists (doctors who specialize in genetics), neurologists, neuro-oncologists and other providers can monitor for possible complications, manage a child’s symptoms and help them experience the best quality of life possible.

Neurofibromatosis 2

Neurofibromatosis 2 is a genetic disorder that causes slow-growing tumors on the eighth cranial nerves and other nerves located in the brain and spine. It can result in hearing loss, vision loss and other concerns.

Neurofibromatosis 2 is rare, affecting about 1 in every 25,000 people. A genetic change on chromosome 22 causes NF2.

Neurofibromatosis 2 Signs and Symptoms

Children and adults with neurofibromatosis 2 may have one or more types of slow-growing tumors on the nerves of their brain and spinal cord. These tumors usually are not cancerous, but they can cause problems depending on their location. For example, tumors in the inner ear can cause hearing loss. Tumors on the spinal cord can cause muscle weakness or paralysis.

The most common type of tumor in people with NF2 is a vestibular schwannoma (sometimes called an acoustic neuroma). These tumors occur on the main nerve leading from the inner ear to the brain. They usually begin to cause problems in the late teen to early adult years. Some people with NF2 eventually lose their hearing in one or both ears.

Children with NF2 also may have:

• Other types of tumors. These include meningiomas, ependymomas and schwannomas. Children with neurofibromatosis 2 do not develop plexiform neurofibromas that are common in children with neurofibromatosis 1.
• A cataract. This is a cloudy lens that forms on the back of the eye.
• Café-au-lait spots. Most people with NF2 only have a few of these, unlike patients with NF1, who have many.

Signs and symptoms of neurofibromatosis 2 vary in severity and can include:

• Gradual hearing loss
• Ringing in the ears
• Balance problems
• Headaches
• Numbness and weakness in the arms or legs
• Pain
• Vision problems due to cataracts

Neurofibromatosis 2 Diagnosis

Neurofibromatosis 2 Treatment

Treatment for neurofibromatosis 2 focuses on treating the tumors with surgery, chemotherapy or both. Some surgeons have had success in preserving hearing by operating on vestibular schwannomas while the tumors are still very small. The care team will typically recommended that people with NF2 (and their family members) start learning sign language while they still have hearing, because of the high risk of deafness.

Neurofibromatosis 2 is a chronic (long-term) condition and can cause serious complications. Pediatric geneticists, neurologists, neuro-oncologists, oncologists (doctors who treat tumors) and others who specialize in neurofibromatosis can provide individualized treatment to help children with NF2 experience the best quality of life possible.

Schwannomatosis

Schwannomatosis is a rare form of neurofibromatosis that usually affects people after age 20. Patients with schwannomatosis develop multiple schwannomas (Schwann cell tumors) on different parts of their bodies, such as their:

• Cranial, spinal and peripheral nerves
• Arms
• Legs
• Chest
• Abdomen

These tumors are not cancerous, but they often are painful. In the large majority of cases, schwannomatosis is not a life-threatening disorder.

Some people have “partial” or “mosaic” forms of schwannomatosis, which are less severe than fuller forms of the disease. These people will only have tumors in one area of their body, such as one limb.

Schwannomatosis Diagnosis and Treatment

People who have schwannomatosis usually aren’t aware of their condition until young adulthood, when they start to notice tumors under their skin. Since the signs and symptoms of schwannomatosis are similar to those of neurofibromatosis 2, genetic testing is critical to confirm the diagnosis.

Schwannomatosis usually is not life-threatening, but people with this condition need treatment to manage the tumors and pain. The tumors sometimes can be removed with surgery, but there isn’t yet a drug that can shrink them.

Legius Syndrome

Legius syndrome is a rare, recently diagnosed disorder whose features overlap with those of neurofibromatosis 1. It is due to a change in a gene called SPRED1. Patients with Legius syndrome may have:

• Café-au-lait (light brown) spots on the skin
• Armpit freckling
• Learning disabilities

Children with Legius syndrome don’t develop tumors. Genetic testing can confirm a diagnosis of Legius syndrome. The condition typically causes mild symptoms. Many people with Legius syndrome are never aware they have it.