Neurofibromatosis is a rare genetic disorder, which causes usually benign nerve tumors and growths located in other areas of the body. Certain people with this disorder barely experience noticeable neurological problems, while other patients are profoundly affected. Two major types exist: neurofibromatosis type I (NF1) and neurofibromatosis type II (NF2).
NF1 manifests itself at birth or during a patient’s early childhood. NF1 is characterized by multiple light brown (café-au-lait) spots, which concentrate in the groin and underarms, along with benign tumors under the skin. Enlargement and deformity of bones and curvature of the spine (scoliosis) can also present.Sometimes, people with NF1 can develop tumors on the cranial nerves, in the brain, or involving the spinal cord.
NF2 can appear during childhood, adolescence, or early adulthood. This condition is primarily characterized by benign nerve tumors, which transmit sound impulses and balance signals from the inner ears to the brain. Tumors often affect both the left and right (“bilateral”) auditory (hearing) nerves.
A third related disorder, known as schwannomatosis, is recognized. Schwannomatosis can share many features with NF1 and NF2, but current evidence suggests that it is its own distinct genetic disease. It is more frequently diagnosed in adults aged 30+.
CAUSES
Mutations in the gene that controls production of a protein and acts as a tumor suppressor (neurofibromin [neurofibromin 1]) causes this. In about 50% of people affected by NF1, the disorder results from gene mutations, which occur for unknown reasons (“spontaneous mutation”). In other patients with the disorder, NF1 is inherited through autosomal dominant inheritance.
NF2 results from mutations in another tumor-suppressing gene (neurofibromin 2, merlin). Certain people with NF2 are affected by a gene mutation that occurs for unknown reasons (“spontaneous mutation”), while others inherit it from their parent(s) through an autosomal dominant inheritance pattern.
While schwannomatosis is not understood well, about 85% of cases hold no known cause (“spontaneous”), while 15% are inherited.
INCIDENCE AND PREVALENCE
- NF1 occurs in about one out of every 3,500 births
- NF2 occurs in about one out of every 40,000 births
- Schwannomatosis occurs in about one out of every 40,000 births
- There is a 50% chance that each child of a parent with NF1 or NF2 will inherit the gene and develop NF1 or NF2 (autosomal dominant inheritance)
- Tumors typically benign (malignant in about 3-5% of all cases)
- About ⅓ of people with NF notice no symptoms
OTHER NAMES
Neurofibromatosis Type I (NF1)
- Von Recklinghausen’s Disease
- Neurofibroma, multiple
- Neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome
- Von Recklinghausen’s Phakomatosis
- Von Recklinghausen’s Neurofibromatosis
- Peripheral Neurofibromatosis
Neurofibromatosis Type II (NF2)
- Bilateral Acoustic Neurofibromatosis
- Central Neurofibromatosis
- Vestibular Schwannoma Neurofibromatosis
DIAGNOSTIC CRITERIA/SIGNS OF NF1
- NF1 family history
- 6+ café-au-lait spots on the skin
- Larger areas on/under the skin that seem swollen (plexiform neurofibromas)
- Pigmented bumps on the eye’s iris (Lisch nodules)
- Skeletal abnormalities, like bowing of the legs (tibial dysplasia), thinning of the shin bone, scoliosis
- Freckling under the arms or in groin area
- Presence of pea-sized bumps (neurofibromas) on or just under the skin
- Tumor on the optic nerve that can interfere with vision
Café-au-lait spots most commonly appear on the chest, back, pelvis, elbows and knees. These spots can exist at birth or appear during one’s infancy. Between ages 10-15, flesh-colored growths of different shapes and sizes can begin to appear on the skin. There can be fewer than 10 of these growths or thousands of them.
Other features can include an unusually large head (macrocephaly) and relatively short stature. Seizures can occur, learning disabilities, speech problems or hyperactivity can be experienced by patients.
DIAGNOSTIC CRITERIA/SIGNS OF NF2
- Bilateral vestibular schwannomas (VS) (known as acoustic neuromas) are definitive signs of NF2
- Probable signs of NF2 include family history of NF2, unilateral VS, or any two of the following conditions (meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, juvenile cortical cataracts)
Depending upon the exact location and size of the VS, any of the following can occur, either alone or in combination with each other
- Balance problems
- Walking problems
- Hearing loss
- Facial weakness
- Numbness or pain
- Ringing in ears (tinnitus)
- Dizziness
- Headache
DIAGNOSTIC CRITERIA/SIGNS OF SCHWANNOMATOSIS
- Definitive signs (age 30+) include showing no evidence of vestibular tumors on an MRI, containing no known NF2 mutation, and holding two+ schwannomas within or between layers of skin (with at least one schwannoma confirmed by tissue pathology)
- One pathologically confirmed schwannoma and a first-degree relative who meets the above criteria is also a definitive sign of schwannomatosis
- About ⅓ of those with schwannomatosis contain segmental schwannomatosis with tumors limited to one section of the body (such as an arm, leg or a region of the spine)
TREATMENT AND MANAGEMENT
Children who have NF1 should be checked for height, signs of learning disability, weight, evidence of normal sexual development, head circumference, and/or behavioral issues. These children should receive an examination of the skin for growths, spots, scoliosis, blood pressure, vision, and screening for hearing loss. Unusual growth patterns are usually investigated. Early or late onset of puberty also can suggest further study. Diagnostic evaluations like blood tests and X-rays can be ordered if additional concerns exist. Healthy children who have NF1 are generally examined at six or 12-month intervals.
Adults who have NF1 often have standard physical evaluations, as well as an examination of the skin for growths, spots, scoliosis, blood pressure, vision, and screening for hearing loss. Physicians should also stay vigilant on the search for any new or enlarging mass or any new symptoms in general. Otherwise healthy adults with NF1 typically have annual checkups.
No known treatment or cure for neurofibromatosis exists. None for schwannomatosis exist, either. In certain instances, growths can be removed surgically or reduced with radiation therapy. Surgery in such areas can cause further injury to nerves and additional neurological problems, as benefits of surgery should be weighed against its risks. Likewise, in situations where radiation treatment is an option, the risks and benefits must be carefully considered.
