Neurofibromatosis

Neurofibromatosis is a rare genetic disorder that causes benign tumors of the nerves and growths in other parts of the body. Some people with this disorder have barely noticeable neurological problems, while others are affected profoundly. There are two primary types: neurofibromatosis Type 1 (NF1), and neurofibromatosis Type 2 (NF2).

NF1 manifests itself at birth or during early childhood. NF1 is characterized by multiple light brown (cafe-au-lait) spots and benign tumors on or under the skin. Enlargement and deformation of bones and curvature of the spine (scoliosis) may also be present. On occasion, people with NF1 may develop tumors in the brain, on cranial nerves, or on the spinal cord.

NF2 may first appear during childhood, adolescence or early adulthood. NF2 is primarily characterized by benign tumors of the nerves that transmit sound impulses from the inner ears to the brain. Tumors commonly affect both of the auditory nerves.

A third related disorder, called schwannomatosis has recently been recognized. While schwannomatosis shares many features with NF1 and NF2, current evidence suggests that it is a distinct genetic disease. This disorder is more frequently diagnosed in adults age 30 and older.

Causes and Risk Factors

NF1 is caused by mutations in the gene that controls production of a protein called neurofibromin. This gene is believed to function as a tumor suppressor. In about 50 percent of people with NF1, the disorder results from gene mutations that occur for unknown reasons. In others with the disorder, NF1 is an inherited trait.

NF2 results from changes in a different tumor-suppressing gene. Some people with NF2 experience a gene mutation that occurs for unknown reasons, while others inherit the trait.

While schwannomatosis is not well understood, it is estimated that 85 percent of cases have no known cause and 15 percent are inherited.

Incidence and Prevalence

  • NF1 occurs in an estimated one out of every 3,500 births
  • NF2 occurs in an estimated one out of every 40,000 births
  • Schwannomatosis occurs in an estimated one out of every 40,000 births
  • There is a 50 percent chance that each child of a parent with NF1 or NF2 will inherit the gene and develop NF1 or NF2
  • Tumors become malignant in only 3 to 5 percent of all cases
  • About one-third of people with neurofibromatosis notice no symptoms

Other Names

Neurofibromatosis Type 1 (NF1)

  • Recklinghausen's phakomatosis
  • Von Recklinghausen's disease
  • Von Recklinghausen's neurofibromatosis
  • Neurofibroma, multiple
  • Neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome
  • Peripheral neurofibromatosis

Neurofibromatosis Type 2 (NF2)

  • Bilateral Acoustic Neurofibromatosis
  • Central Form, Neurofibromatosis
  • Vestibular Schwannoma Neurofibromatosis

Diagnostic Criteria/Signs of NF1

  • Family history of NF1
  • Six or more cafe-au-lait spots on the skin
  • Presence of pea-sized bumps (neurofibromas) on the skin
  • Larger areas on the skin that appear swollen (plexiform neurofibromas)
  • Freckling under the arms or in the groin area
  • Pigmented bumps on the eye's iris (Lisch nodules)
  • Skeletal abnormalities such as bowing of the legs (tibial dysplasia) or thinning of the shin bone
  • Tumor on the optic nerve that may interfere with vision

Café au lait spots are most common on the chest, back, pelvis, elbows and knees. These spots may exist at birth or appear during infancy. Between ages 10 and 15, flesh-colored growths of different sizes and shapes may begin to appear on the skin. There may be fewer than 10 of these growths or thousands of them.

Additional characteristics may include an unusually large head (macrocephaly) and relatively short stature. Other abnormalities may include seizures, learning disabilities, speech problems, and hyperactivity.

Diagnostic Criteria/Signs of NF2

Bilateral vestibular schwannomas (VS), also called acoustic neuroma, is a definitive sign of NF2.

Probable signs of NF2 include a family history of NF2 and unilateral VS or any two of the following: meningiomas, gliomas, schwannomas, juvenile posterior subcapsular lenticular opacity, juvenile cortical cataracts.

Depending on the exact location and size of the VS, any of the following may occur, alone, or in combination:

  • Balance disturbances
  • Walking disturbances
  • Dizziness
  • Headache
  • Facial weakness
  • Numbness or pain
  • Ringing in the ears
  • Progressive hearing loss

Diagnostic Criteria/Signs of Schwannomatosis

Definitive signs include being age 30 and older and showing no evidence of vestibular tumors on magnetic resonance imaging (MRI), having no known NF2 mutation, and having two or more schwannomas within or between layers of the skin; at least one that is pathologically confirmed. One pathologically confirmed schwannoma and a first degree relative who meets the above criteria is also a definitive sign of schwannomatosis.

About one-third of people with schwannomatosis have segmental schwannomatosis, with tumors limited to one part of the body, such as an arm, a leg or a region of the spine.

Treatment and Management

Children with NF1 should be checked for height, weight, head circumference, evidence of normal sexual development, signs of learning disability and hyperactivity. They should receive an examination of the skin for growths/spots, and spine for scoliosis, and blood pressure, vision and hearing screenings. Any unusual growth patterns are generally investigated. Early or late onset of puberty also may indicate further study. Diagnostic evaluations such as blood tests and x-rays may be ordered if there are additional problems. Healthy children with NF1 are usually examined at six or 12-month intervals.

Adults with NF1 generally have standard physical evaluations and an examination of the skin for growths/spots, and spine for scoliosis, and blood pressure, vision and hearing screenings. The doctor will look for any mass that is rapidly enlarging or causing new pain. Other tests can be performed if a medical problem develops. Adults with NF1 who are otherwise healthy usually have periodic check-ups annually.

There is no known treatment or cure for neurofibromatosis. In some cases of NF2, growths may be removed surgically or reduced with radiation therapy. Surgery in these areas may cause further injury to nerves and additional neurological problems. The benefits of surgery should always be weighed carefully against its risks. When surgery is no longer an option because of medical problems or the size or location of a tumor, radiation therapy may be considered. As with surgery, radiation therapy has both risks and benefits which must be carefully considered.

There is no currently accepted medical treatment or drug for schwannomatosis. The tumors are relatively slow growing, and may only need to be imaged when symptoms change. When tumors are completely removed surgically, pain often subsides, but may recur if new tumors form. When surgery is not possible, management in a multidisciplinary pain clinic may be recommended.

Source: The American Association of Neurological Surgeons

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