What is neurofibromatosis type 2?
Neurofibromatosis type 2 (NF2), also called NF2-related schwannomatosis, is a hereditary condition most commonly associated with bilateral vestibular schwannomas, also known as acoustic neuromas. These are benign (noncancerous) tumors that occur on the nerves for balance and hearing leading to the inner ear. Although these tumors are benign, they can cause hearing and balance problems.
People affected by NF2 also have an increased risk of other tumors of the nervous system. These tumors are generally benign, but they may still lead to significant medical problems, especially if there are multiple tumors in or next to the brain. Other nervous system tumor types include:
Schwannomas of other nerves
Meningiomas, a slow-growing tumor that usually develops on the surface of the brain
Gliomas, including ependymomas of the brain or spinal cord
People with NF2 are at an increased risk of developing cataracts in the eyes and benign skin tumors. They may have café-au-lait spots, which are light brown pigmentation, the color of “coffee with milk”. This feature is similar to those individuals with Neurofibromatosis Type 1, but people with NF2 usually have fewer café-au-lait spots than people with NF1.
Signs of NF2 usually develop in the late teenage years or early 20s. Multiple features have been associated with NF2, but the overall cancer risk is low. The number of features present and the severity of symptoms can vary among people with NF2, even within the same family.
What causes NF2?
NF2 is a genetic condition. This means that the cancer risk and other features of NF2 can be passed from generation to generation in a family. The gene associated with NF2 is also called NF2. The gene is noted in italics to help distinguish the gene from the condition. A mutation (alteration) in the NF2 gene, which is a “tumor suppressor,” gives a person an increased risk of developing cancerous and benign tumors and other symptoms of NF2. Most people with NF2 have a mutation in the NF2 gene. Research is ongoing to learn more about the causes of NF2.
How is NF2 inherited?
Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. NF2 follows an autosomal dominant inheritance pattern, in which a change, also called a mutation or alteration, happens in only 1 copy of the gene. This means that a parent with an NF2 mutation may pass along a copy of their normal gene or a copy of the changed gene. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk.
Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. Eggs are removed from the ovaries and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos which do not have the mutation. PGD has been in use for over 2 decades and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.
How common is NF2?
It is estimated that about 1 in 40,000 people has NF2. About 50% of people affected by NF2 do not have any family history of the condition. They have a de novo (new) mutation in the NF2 gene.
How is NF2 diagnosed?
Many sets of diagnostic guidelines have been suggested for NF2, and future revisions are likely. The features are very specific, and it is important to have a careful evaluation by a doctor who has experience with NF2 to make the diagnosis. In general, someone is suspected of having NF2 if they have any of the following:
Bilateral (meaning both sides) vestibular schwannomas, which are tumors that grow from the nerve that controls hearing and balance
A parent, sibling, or child with NF2 and either of the following:
A single vestibular schwannoma diagnosed before age 30, or
Any 2 of the following: a meningioma, glioma, schwannoma, or cataract
A single vestibular schwannoma diagnosed before age 30 and a meningioma, glioma, schwannoma, or cataract
Multiple meningiomas and a unilateral, meaning affecting only 1 side vestibular schwannoma diagnosed under age 30, a glioma, schwannoma, or cataract.
Genetic testing for mutations in the NF2 gene is available for people diagnosed with NF2.
What are the estimated cancer risks associated with NF2?
Tumors associated with NF2 are usually benign. The lifetime risk of cancer in a person with NF2 is considered to be low.
What are the screening options for NF2?
Suggested screenings for people with NF2 or at risk for NF2 include:
A yearly magnetic resonance imaging (MRI), beginning in the teenage years
Hearing evaluations, including audiometry and a brain stem auditory evoked response (BAER) test, which is a test that detects electrical activity in the cochlea and auditory pathways
Screening recommendations may change over time as new technologies are developed and more is learned about NF2. It is important to talk with your health care team about appropriate screening tests. In some areas, comprehensive NF2 clinics may be available to help with coordination of medical care.
Learn more about what to expect when having common tests, procedures, and scans.
How are tumors related to NF2 treated?
The primary method of treating tumors associated with NF2 is surgery. At the same time, many people with this disease have tumors that grow slowly or not at all. That means they can be closely monitored in an approach called watchful waiting, watch and wait, or active surveillance. In this approach, active treatment would begin if there are signs that the tumor could cause neurological problems (problems with the brain, nerves, or spinal cord), or the pattern of growth threatens brain or spinal cord function.
Specifically regarding bilateral acoustic neuromas, a major goal of treatment is to preserve the person’s hearing for as long as possible. However, hearing will eventually be lost at some point. Surgery is usually done in people who can no longer hear or in those with a small tumor where a meaningful attempt can be made at preserving the nerve that makes hearing possible.
In addition, focused radiation therapy is sometimes used for vestibular schwannomas. Like surgery, it carries a risk that the treatment will hurt the person’s hearing in order to control the tumor.
Reports of using bevacizumab (Avastin), a drug that interferes with blood vessel formation to stop tumor growth, for treating vestibular schwannomas associated with NF2, have been encouraging. Although only a few people have been treated with this drug, the results include both measurable shrinkage of tumor and partial restoration of hearing loss in some, but not all, patients. This is an experimental treatment and needs more testing, but it holds promise that other drugs may be proven effective as well. Talk with your health care team about this option, including the side effects of bevacizumab. In addition, you should ask about available clinical trials, which are research studies looking for new treatments.
The other tumors seen in this disease are usually meningioma and ependymoma, and these types are typically removed only if they grow to an extent that they put enough pressure on the nearby brain or spinal cord to affect its functioning.
Questions to ask the health care team
If you are concerned about your risk of cancerous and benign tumors from NF2, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:
What is my risk of developing tumors of the nervous system?
What can I do to reduce my risk of this?
What are my options for screening?
If you are concerned about your family history and think you or your other family members may have an NF2 mutation, consider asking the following questions:
Does my family history increase my risk of developing cancer?
Does it suggest the need for a cancer risk assessment?
Will you refer me to a genetic counselor or other genetics specialist?
Should I consider genetic testing?
To find a genetic counselor in your area, ask your health care team or visit this website: