Neurofibromatosis Type 2

Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by certain types of tumors that form within a person’s body or brain. NF2 causes slow-growing tumors to develop on the eighth cranial nerve, which is located in the inner ear.

The most common types of tumors associated with NF2 are:

• Vestibular schwannoma: Also called an acoustic neuroma, a vestibular schwannoma is a benign (non-cancerous) tumor that develops on the eighth cranial nerve (a nerve in the inner ear responsible for hearing and balance).
• Meningioma: Usually benign, a meningioma is a type of tumor that develops from the meninges (the membrane that surrounds the brain and spinal cord). Meningiomas may cause seizures, hemiparesis (weakness on one side of the body), changes in vision, and headaches that worsen over time.
• Ependymoma: A type of brain tumor that develops from ependymal cells that line the ventricles (fluid-filled spaces in the brain) and the central canal within the spinal cord. These tumors often cause problems such as numbness, weakness, and pain.

Besides NF2, there are two other distinct forms of neurofibromatosis: neurofibromatosis type 1 (NF1) and schwannomatosis.

NF2 occurs in about one in every 35,000 births and affects both sexes equally. In 50 percent of cases, NF2 is inherited from a parent. The other half of the time, NF2 occurs as a result of a spontaneous mutation. It is usually detected in early adulthood, with the average age of symptom onset being around 20 years.

There is no known cure for NF2, but much can be done in terms of managing symptoms. The majority of children with NF2 will lead relatively normal and productive lives.

Because NF2 affects the nervous system, the most complications involve problems related to vision, hearing, and balance. Numbness or weakness in the face, arms, or legs may also occur.  There is no evidence that NF2 causes intellectual and learning disabilities, which are very common in individuals with NF1.

The first symptoms of NF2 are usually caused by the eighth cranial nerve’s impairment:

• Hearing loss
• Ringing in the ears (tinnitus)
• Problems with balance, beginning in the teens or early 20s

Other symptoms of NF2 may include:

• Facial weakness
• Headache
• Changes in vision
• Cataracts
• Back pain (caused by spinal cord lesions)
• Skin changes (caused by schwannomas on the skin, which is more common in children)

Although it’s almost impossible to predict exactly how NF2 will progress, vestibular schwannomas grow slowly and usually cause balance and hearing to deteriorate over time. There are surgical interventions that can preserve hearing.

In 50 percent of cases, NF2 is inherited from a parent: During conception, each parent passes on a copy of the NF2 gene to the embryo. Since NF2 is an autosomal dominantgenetic disorder, the child will inherit the disorder if just one of these genes has a mutation. With each pregnancy, parents who are affected by NF2will themselves have a 50 percent chance of passing it on to their child. NF2 affects people of all races, sexes and ethnicities equally.

In the other 50 percent of cases, NF2 occurs as a result of a spontaneous mutation that occurs when there is a sudden change in genetic material at the time of conception. Spontaneous mutations occur in situations where there is no prior family history of NF.

In order to have a confirmed diagnosis of NF2, an individual must have a bilateral vestibular schwannoma (affecting both ears); a first-degree family relative who has NF2 and a unilateral vestibular schwannoma (affecting one ear) that presents before the age of 30 years; or a first-degree family relative who has NF2 and any two of the following:

• Neurofibroma
• Glioma
• Meningioma
• Schwannoma
• One of two types of cataracts seen in children: the juvenile posterior subcapsular lenticular opacity or the juvenile cortical cataract (these are seen only by the ophthalmologist)

Doctors may use a magnetic resource-imaging scan (MRI) to look for vestibular schwannomas or other tumors associated with NF2, especially if there is a family history of the disorder. Individuals without a family history but suspected to have NF2 are evaluated in a similar way with imaging studies and regular hearing evaluations.

If an individual meets the diagnostic criteria for NF2, the doctor might also use genetic testing to confirm the diagnosis. However, these tests often aren’t necessary to confirm a diagnosis.

A person with NF2 might need one or more of the following treatment methods to manage symptoms:

• Surgery: Surgery may be used to remove schwannomas that are pushing on the spinal cord or meningiomas (a non-cancerous tumor) that are causing seizures. We take a more conservative approach to treating tumors. We only use surgery in situations where the tumor is producing symptoms and causing problems.
• Medication: Medication can also sometimes be useful in managing your child's symptoms; for example, if she's experiencing tinnitus, headaches, or pain caused by tumors pressing on her nerves.
• Physical therapy: Children with NF2 may have a tumor pushing on the cerebellum (the part of brain that controls balance). These tumors usually need to be surgically removed in order for the problem to be eliminated. However, physical therapy (PT) can compensate for problems with balance and weakness by helping to strengthen the core muscles. PT can also help children with NF2 learn how to be more careful when their walking so they won't fall.
• Supportive devices: Hearing aids or an FM system may be recommended for use if there is documented decrease in hearing.

Individuals who experience hearing loss or impairment have the following non-surgical treatment options:

• Lip reading
• Sign language
• Hearing aids
• Cochlear implants

The Multidisciplinary Neurofibromatosis Program at Boston Children’s Hospital is one of the oldest and largest neurofibromatosis clinical programs in the United States. Our clinic brings together specialists from a variety of departments throughout the hospital to provide expert diagnosis, evaluation, and treatment, along with counseling, support, and education services.

After an adolescent or young adult has been diagnosed with NF2, our doctors will see her at least once per year and arrange more frequent follow-up visits if necessary.

Genetic counselors are available to explain the possible genetic and hereditary implication of NF2 for affected individuals and their family members.

The most unique feature of our program is that it brings together physicians from various departments who have many years of experience diagnosing and treating NF. This multidisciplinary approach allows us to provide you with direct connections to experts specializing in:

• Ophthalmology
• Otolaryngology (ear, nose, throat)
• Neurology
• Neurosurgery
• Plastic surgery
• General surgery
• Audiology

The Neurofibromatosis Program is one of the few sites that’s part of a national neurofibromatosis (NF) clinical trials consortium. Any new clinical trials opening in the area of NF1 or NF2 will involve our program.

We’re moving into a whole new era of medicine that features targeted treatments for individuals with NF2.  For the first time these treatments, as part of clinical trials, will be available in children.

The national NF clinical trial consortium, funded by the U.S. Department of Defense, includes some of the largest NF centers throughout the country, both for NF1 and NF2. The goal of this consortium is to create targeted treatments for the various types of tumors accompanying NF and related disorders.

If you’d like to find out more about our research and clinical trials or see whether your child might be a candidate, please talk to your child’s doctor or email us at nf@childrens.harvard.edu.