Neurofibromatosis types 1 and 2 (NF1 and NF2) are genetic disorders. NF1 and NF2 are different conditions. They are frequently discussed together and often confused for one another. Both disorders have widely variable presentations and degrees of severity. Each one will be described separately.
Neurofibromatosis type 2 (NF2) is relatively rare, affecting approximately 1 in 25,000 people. Though it is a genetic condition, it is only sometimes inherited in families. The hallmark feature of NF2 is the growth of benign tumors called vestibular schwannomas on both the nerves responsible for carrying information about sound and balance from the inner ear to the brain. People with NF2 may also develop benign growths of other nerves. About half of those affected with NF2 will have other affected family members. NF2 follows a clear autosomal dominant inheritance pattern, meaning that if a parent is affected, there is a 50 percent chance for each child being affected with NF2. Often with autosomal dominant conditions, you will see the disease in every generation of a family.The remaining half of those affected with NF2 will be the only members in their family who have the condition, and will have no other affected family members. This is a result of spontaneous gene mutation that occurs at the moment of conception for reasons that are not clear. Interestingly, 25-30 percent of those individuals who are the only family members affected are considered to be mosaic for NF2. In other words, only some cells in their body (i.e., the nerves to the ear or vestibular nerve) have the gene mutation that causes NF2, while other cells do not. Sometimes, it turns out that one of the parents has the gene mutation that causes NF2; however, for some reason they never developed any tumors of the nerve to the ear and have lived without any symptoms.
The gene for NF2 has been identified and is located on the long arm of chromosome 22; specifically 22q12.2.
Most commonly, the first symptoms of NF2 are symptoms of dysfunction of the vestibular nerve, which carries information about sound and balance to the brain. Consequently, hearing loss, tinnitus (ringing in the ears), and problems with balance arise, usually beginning in the teens or early twenties. The average age of symptom onset in patients with NF2 is between 18-24 years, while the average age of diagnosis is at about age 28. Almost all affected persons develop bilateral vestibular schwannomas by 30 years of age.
Other symptoms of NF2 may include facial weakness, headache, change in vision, and a lump or swelling under the skin caused by the development of a schwannoma. Unlike patients with NF1, it is not common to have café-au-lait spots (brown spots or birthmarks on the skin); however sometimes there may be one or two spots present.
People with NF2 are at increased risk to develop other types of nervous system tumors throughout their life. Schwannomas may also develop on other nerves in the brain and body, with sensory nerves more frequently involved than motor nerves. These include:
Spinal tumors - Approximately half of individuals with NF2 develop meningiomas during their lifetime. Meningiomas are typically benign tumors arising from the meninges, a fibrous sac encompassing the brain and spinal cord.
Meningioma - These are benign tumors that are present in the covering of the nerve cells. There are three main types of neurofibromas: cutaneous, subcutaneous and plexiform.
Ocular involvement - One-third of individuals with NF2 have decreased visual acuity in one or both eyes. A typical cataract is the most common ocular finding. Lens opacities may appear prior to the onset of symptoms from vestibular schwannoma and can be seen in children with NF2.
The National Institutes of Health released a set of criteria in 1987 which has recently been modified. According to the modified criteria, NF2 is diagnosed in individuals with one of the following:
Currently, the diagnosis of NF2 is typically made based on physical findings and results of brain and spine scans. Genetic testing through a blood test is also available but, generally, will not assist in making the diagnosis. Current genetic testing has limitations, as laboratory technology is not able to determine with 100 percent accuracy the presence of a gene mutation. Testing is currently 95 percent accurate. For those who proceed with genetic testing, if no gene mutation is identified, NF2 is still a possible diagnosis. If a gene mutation is identified, the diagnosis is confirmed.
For those individuals who have a diagnosis of NF2, monitoring through Magnetic Resonance Imaging (MRI) is necessary for the vestibular schwannomas. At times, surgery, and sometimes radiation therapy, is necessary. Hearing loss is a common complication of NF2; people with NF2 typically undergo hearing (audiologic) testing at least every year. Those diagnosed with NF2 are encouraged to learn sign language and/or lip reading prior to losing their hearing ability For those individuals who are felt to be at risk, certain monitoring is recommended. Depending on the family history, monitoring through MRI can start as early as 10-12 years of age. This can also be later in some families if the age of onset is felt to be later. In general, an MRI is completed every year until the fourth decade of life. Although some individuals with NF2 do not have symptoms until they are in their fifties, it is likely that "silent" tumors would be detected on an MRI performed at a younger age. In some situations, hearing evaluations can also be beneficial.
It is important to remember that often information found on the Internet can be incorrect, biased and sometimes very scary. NF2 has a variety of features and symptoms. Often Internet sites focus on sharing the worst case scenarios. For non-biased, medically sound information on NF2, helpful resources include:
Children's Tumor Foundation, which is dedicated to NF research and information/support http://www.ctf.org/camp/
Neurofibromatosis Inc., a national support and advocacy group www.nfinc.org
NF2 Crew, a support group for NF2 www.nf2crew.org
Acoustic Neuroma Association, support and information for patients, families and medical professionals www.anausa.org
Comprehensive Neurofibromatosis Clinic
NewYork-Presbyterian Komansky Center
for Children's Health
505 East 70th Street
Helmsley Tower, 3rd floor
New York, NY 10021
Phone: (212) 746-3278
Fax: (212) 746-8137