Neurofibromatosis

What Is Neurofibromatosis?

Neurofibromatosis is a genetic disorder of the nervous system. Tumors form on your nerve tissues. Mainly, neurofibromatosis disorders affect the growth and development of nerve cell tissue. The disorders are known as neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). NF1 is the more common type of neurofibromatosis. Schwannomatosis has recently been identified as a third and more rare type of neurofibromatosis, but doctors don’t know much about it yet.

You may also hear NF1 called Recklinghausen disease, von Recklinghausen disease, von Recklinghausen’s phakomatosis, von Recklinghausen’s neurofibromatosis, neurofibroma (multiple), neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome, or peripheral neurofibromatosis. It causes multiple café au lait spots (patches of tan or light brown skin) and neurofibromas (soft, fleshy growths) on or under your skin. It can also cause enlarged or deformed bones and curvature of the spine (scoliosis). Occasionally, tumors may develop in the brain, on cranial nerves, or on the spinal cord. About 50% to 75% of people with NF1 also have learning disabilities.

NF2 is also called bilateral acoustic neurofibromatosis, vestibular schwannoma neurofibromatosis, or central neurofibromatosis. It’s much less common than NF1 and is characterized by multiple tumors on the cranial and spinal nerves. Tumors that affect both of the auditory nerves and hearing loss beginning in the teens or early 20s are generally the first symptoms of NF2.

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Neurofibromatosis Symptoms

Neurofibromatosis 1 (NF1) symptoms

The following symptoms appear in people with NF1:

  • Several (usually 6 or more) café au lait spots
  • Multiple freckles in the armpit or groin area
  • Tiny growths in the iris (colored area) of the eye; these are called Lisch nodules and usually do not affect eyesight.
  • Neurofibromas that occur on or under the skin, sometimes even deep within the body. These are benign (harmless) tumors. But in rare cases, they can turn malignant or cancerous.
  • Bone deformities, including a twisted spine (scoliosis) or bowed legs
  • Tumors along the optic nerve, which may cause eyesight problems
  • Nerve-related pain
  • High blood pressure
  • Osteoporosis
  • Learning disabilities
  • Large head size
  • Short stature

Neurofibromatosis 2 (NF2) symptoms

People with NF2 often display the following symptoms:

  • Loss of hearing
  • Weakness of the muscles of the face
  • Dizziness
  • Poor balance
  • Uncoordinated walking
  • Cataracts (cloudy areas on the lens of the eye) that develop at an unusually early age
  • Headaches

Schwannomatosis symptoms

People with schwannomatosis may have the following symptoms:

Neurofibromatosis Causes

Neurofibromatosis is often inherited (passed on by family members through your genes). But about 50% of people newly diagnosed with the disorder have no family history of the condition. That’s because it can result from a sudden mutation (change) in your genes. Once this change takes place, you can pass the mutant gene on to future generations. Mutations that lead to neurofibromatosis include:

  • Neurofibromatosis 1 (NF1): The NF1 gene on chromosome 17 makes a protein called neurofibromin that controls your cells’ growth. The mutation of this gene causes a neurofibromin loss and uncontrolled cell growth.
  • Neurofibromatosis 2 (NF2): The NF2 gene on chromosome 22 makes a protein called merlin or schwannomin. It suppresses tumors. Changes to this gene cause a loss of merlin and uncontrolled cell growth.
  • Schwannomatosis: Mutations of the two known genes linked to schwannomatosis, SMARCB1 and LZTR1, which both suppress tumors, are associated with this type of neurofibromatosis.

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Neurofibromatosis Diagnosis

Neurofibromatosis is diagnosed using a number of tests, including:

To receive a diagnosis of NF1, you must have two of the following features:

  • Six or more café au lait spots that are 1.5 centimeters or larger in people who have had puberty, or 0.5 centimeters or larger in people who haven’t
  • Two or more neurofibromas (tumors that develop from the cells and tissues that cover nerves) of any type, or one or more plexiform neurofibroma (a nerve that has become thick and misshapen due to the abnormal growth of cells and tissues that cover the nerve)
  • Freckling in the armpit or groin
  • Optic glioma (tumor of the optic pathway)
  • Two or more Lisch nodules
  • A distinctive bony lesion, dysplasia of the sphenoid bone, or dysplasia or thinning of long bone cortex
  • A first-degree relative with NF1

To be diagnosed with NF2, you must have:

  • Bilateral (on both sides) vestibular schwannomas, also known as acoustic neuromas. These are benign tumors that develop from the balance and hearing nerves supplying the inner ear.

or

  • Family history of NF2 (first-degree family relative) plus unilateral (on one side) or bilateral vestibular schwannomas, or any two of the following health conditions:
  • Multiple meningiomas (tumors that occur in the meninges, the membranes that cover and protect the brain and spinal cord)
  • Glioma (cancer of the brain that begins in glial cells, which are those that surround and support nerve cells)
  • Any neurofibromas
  • Schwannoma
  • Juvenile cataracts
  • Gradual hearing loss
  • Ringing in the ears
  • Balance problems
  • Headaches

Schwannomatosis diagnosis is based on these criteria:

  • If you’re 30 or older, you have no evidence of vestibular tumors on an MRI scan, no known NF2 gene mutation, and two or more schwannomas within or between skin layers, one being confirmed by a biopsy.
  • You have one schwannoma confirmed by biopsy and a first-degree relative who also meets the criteria.
  • If you have a type called segmental schwannomatosis, you have tumors limited to one area of the body, such as your arm, leg, or spine.

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Neurofibromatosis Treatment

There’s no cure for neurofibromatosis. Treatments focus on controlling symptoms. There’s no standard treatment for NF, and many symptoms, such as café au lait spots, do not need treatment. When treatment is necessary, options may include:

  • Surgery to remove problem growths or tumors
  • Treatment that includes chemotherapy or radiation if a tumor has turned malignant, or cancerous
  • Surgery for bone problems, like scoliosis
  • Therapy (including physical therapy, counseling, or support groups)
  • Cataract removal surgery
  • Aggressive treatment of pain linked to the condition
  • Stereotactic radiosurgery
  • Auditory brainstem and cochlear implants

Neurofibromatosis Complications

Neurofibromatosis complications may vary from person to person. They typically stem from a growing tumor pressing against your nerve tissue or an internal organ.

Possible NF1 complications include:

  • Neurological problems like trouble learning or thinking
  • Anxiety or distress with changes to your appearance, like large numbers of cafe au lait spots
  • Skeletal problems, like bowing of the legs, scoliosis, fractures that don’t heal, or low bone density that increases your risk of osteoporosis
  • Vision problems due to a tumor pressing against the optic nerve
  • Problems during times of hormonal changes, such as puberty or pregnancy
  • Cardiovascular problems like high blood pressure
  • Breathing problems
  • Higher risk of some cancers, such as breast cancer, leukemia, colorectal cancer, brain tumors, and some soft tissue cancers
  • Benign adrenal gland tumor that could cause high blood pressure

Possible NF2 complications include:

  • Partial hearing loss or deafness
  • Nerve damage in the face
  • Benign skin tumors or schwannomas
  • Vision problems
  • Weakness or numbness in your extremities
  • Benign brain or spine tumors that need to be removed with surgery

One possible schwannomatosis complication is severe pain that requires specialist medical treatment or even surgery.

Neurofibromatosis Outlook

Your outlook depends on the type of NF you have. Often, the symptoms of NF1 are mild, and people who have it are able to lead full and productive lives. Sometimes, pain and deformity can lead to significant disability. The NF2 outlook depends on your age at the start of the disease and on the number and location of tumors. Some can be life-threatening.

WebMD Medical Reference Reviewed by Brunilda Nazario, MD on September 28, 2020

Sources

SOURCES:

Ferri, F. Ferri's Clinical Advisor, 1st edition, Mosby, 2013.

National Institute of Neurological Disorders and Stroke.

Neurofibromatosis Type 2 -- Information and Services.

Mayo Clinic: “Neurofibromatosis.”

Genetics Home Reference: “Neurofibromatosis type 1.”

American Association of Neurological Surgeons: “Neurofibromatosis.”

Children’s Tumor Foundation: “Schwannomatosis.”

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