Neurofibromatosis Type 2

A diagnosis of neurofibromatosis type 2 (NF2) comes with many questions and concerns, both for young adults and their families. Although the majority of people with NF2 lead normal lives, there are still many aspects of the disorder that are difficult to predict.

It may comfort you to know that in the Neurofibromatosis Program at Boston Children’s Hospital, we have already helped thousands of children and young adults successfully manage their NF. Our compassionate, experienced clinicians are here to help you every step of the way.

What is NF2?

NF2 is a genetic disorder characterized by certain types of tumors that form within a person’s body or brain.

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. Ependymomas have a 50-percent cure rate.

Are there other types of NF?

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

What is neurofibromatosis type 1 (NF1)?

NF2 may often be confused with NF1. Like NF2, NF1 is also a genetic disorder characterized by the presence of tumors that form along nerves in the body. However, the disorders are caused by two different genes that are located on two different chromosomes. It’s extremely rare that someone would have both NF1 and NF2.

Here are some notable clinical differences between NF1 and NF2: 

• NF2 is more rare than NF1, which affects 1 in every 3,500 births.
• Symptoms of NF2 are typically detected between the ages of 18 and 24 years, while NF1 is diagnosed in infancy or early childhood.
• In NF2, benign tumors called schwannomas grow on nerves throughout the nervous system and often cause impaired hearing and vision. In NF1, benign tumors called neurofibromas cover the peripheral nerve and, similarly, may cause pain or specific neurologic symptoms. Because one type of neurofibroma commonly grows on or close to the skin, there may also be skin changes that range from mild to severe.
• NF2 is caused by a mutation on chromosome 22 and involves a protein called merlin, which is thought to be involved in cell shape and structure. NF1 is caused by a mutation on chromosome 17 and involves a protein called neurofibromin, which relates to cell growth and cell division.
• Individuals with NF2 do not have learning disabilities, a complication that is very commonly seen in people with NF1.

What is schwannomatosis?

Schwannomatosis is an extremely rare form of NF that affects about 1 in every 40,000 individuals. Although schwannomatosis shares some clinical similarities with the other forms of NF, it is a separate disorder.

Here are important distinguishing features of schwannomatosis:

• It is a genetic disorder, but unlike NF1 and NF2, doesn’t have a clear pattern of inheritance. The chance of an affected parent passing schwannomatosis on to their child is 15 percent, compared to 50 percent in NF1 and NF2.
• Schwannomatosis is characterized by the presence of multiple schwannomas (benign tumors) on the cranial, spinal and peripheral nerves. However, unlike with NF2, people with schwannomatosis do not develop vestibular schwannomas and do not experience impaired hearing.
• If a person presents with multiple schwannomas, the possibility of NF2 must excluded before a diagnosis of schwannomatosis is given. Having no evidence of vestibular tumors or family history of NF2 are two diagnostic criteria used for making this distinction.

Are there any medical complications associated with NF2?

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.  However, there is no evidence that NF2 causes intellectual and learning disabilities, which are very common in individuals with NF1.  

Causes

What caused my child to get NF2?

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.
• This means that 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:

• A spontaneous mutation 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.

Is there a difference between inherited NF2 and NF2 that occurs from a spontaneous mutation?

No. Aside from its origins, there is no difference between inherited NF2 and NF2 that was caused by a spontaneous mutation.

Did I do anything to cause my child’s NF2?

No, there’s no evidence suggesting that NF2 is caused by environmental factors or something the mother did (or didn’t do) during pregnancy.

Signs and Symptoms

When do symptoms of NF2 present?

NF2 is usually detected in early adulthood, with the average age of symptom onset being around 20 years.

What are the first signs of NF2?

Most NF2 tumors grow on the eighth cranial nerve. Located in the inner ear, the eighth cranial nerve is responsible for sending information on both sound and balance to the brain.

As a result, the first symptoms of NF2 are usually caused by the nerve’s impairment:

• hearing loss
• ringing in the ears (called tinnitus)
• problems with balance, beginning in the teens or early twenties

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)

Are symptoms of NF2 progressive?

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. Fortunately, there are surgical interventions that can preserve hearing. Visit our Treatment tab to learn more about these options.

Questions to ask your doctor

A diagnosis of NF2 comes with a lot of questions and concerns, for both patients and their families. During your initial appointments with the doctor, it can be easy to become overwhelmed with information and forget what you wanted to ask.

Many parents and young adults find it helpful to write down questions beforehand or jot them down as they arise. That way, when you talk to the doctors, you can be sure that all of your concerns are addressed.

Some questions you might want to ask include:

• How can the symptoms of this disorder be managed?
• What are the options for surgical intervention?
• What is the long-term treatment plan?
• What resources can you point me to for more support and information? 

How is NF2 diagnosed?

 In order to have a confirmed diagnosis of NF2, an individual must have:

• a bilateral vestibular schwannoma (affecting both ears)

OR:

• 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 testsoften aren’t necessary to confirm a diagnosis.

Can NF2 be diagnosed during pregnancy?

If a parent has NF2 and a known mutation, genetic testing can be performed to determine if the baby has inherited the same mutation.

Prenatal diagnosis of NF2 can be done with 65-percent accuracy through:

• chorionic villus sampling (CVS):  CVS is used in situations where there is a known family history of a certain genetic disorder.In this procedure, a sample of chorionic villus cells is taken from the placenta. Since chorionic villi are made up of the same genetic material as the baby, they can be used to test for single gene disorders as well as chromosomal abnormalities. CVS is typically done in the 10^th to 12^th week of pregnancy.
• amniocentesis: In this prenatal diagnosis method, a needle is inserted into the amniotic sac that surrounds the baby and a sample of amniotic fluid is removed. The amniotic fluid contains cells that can be used for genetic testing. Amniocentesis is usually performed between the 15^th and 18th weeks of pregnancy.

When is NF2 diagnosed in individuals who don’t receive prenatal testing?

The age at which a given person is diagnosed with NF2 varies depends on the individual. The average age for diagnosis is 28 years. However, more severe cases of the disorder will be detected earlier than in individuals who show milder symptoms. In familial cases of NF2, if the parental mutation is known, the child can be tested at any age.

How do I know if I should be tested for NF2?

Tell your doctor if you or your child experiences hearing loss, ringing in the ears and problems with balance that begin around age 18 to 24. Since these are usually the first symptoms of NF2, your pediatrician may recommend that you schedule an evaluation with our Neurofibromatosis Program.

How is NF2 treated?

Since a cure for NF2 has not yet been found, treatment focuses on managing symptoms and complications.  Experts here at Children's will customize a comprehensive treatment plan based on each patient's unique needs.

A person with NF2 might need one or more of the following treatment methods in order 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. At Boston Children's, we believe in taking 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 ringing in the ears (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.

How is hearing loss treated?

In most cases, the vestibular schwannomas that grow on the auditory nerve will need to be removed surgically.

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

• lip reading
• sign language
• hearing aids
• cochlear implants

What does long-term follow-up care involve?

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

What makes our approach unique?

In our NF program, the first step in the treatment process is a comprehensive evaluation that includes a physical exam as well as an extensive review of the patient's medical, developmental and family histories. This evaluation will confirm or establish the correct diagnosis of NF2.

Genetic counselors are also 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 throughout Boston Children's 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

What can I do at home to help my child?

The most important things a parent can do for a child who has NF2 is make sure that he is comfortable and safe in his environment, and encourage him to participate in physical therapy and mobility training. Sympathy and emotional support are also invaluable parts of the treatment process.

Coping and support

In our Neurofibromatosis Program, we offer support to adolescents and their families, both online and out in the community.

Our program works to meet the medical and emotional needs of the child as well as the family's needs for support and education. We accomplish this by providing psychosocial counseling and educational materials that address issues related to NF.

Some sources of online support include:

• Children's Tumor Foundation: The Children's Tumor Foundation is a non-profit medical foundation that advocates for research and the development of improved treatment options for NF and related disorders. They also support individuals affected with NF through education and better access to higher-quality health care.
• Neurofibromatosis Network: Neurofibromatosis Network is the leading national organization advocating for federal funding for NF research and the development of local NF organizations
• The NF2 Crew: The NF2 Crew provides online support for individuals with NF2 as well as their friends and families.  Members of the organization occasionally meet up in person to discuss topics and share stories related to the disorder. 

The Neurofibromatosis Program at Boston Children’s Hospital is one of the few sites that’s part of a national neurofibromatosis (NF) clinical trials consortium. This means that any new clinical trials opening in the area of NF1 or NF2 will involve our program here at Boston Children’s.

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.

There is also a national NF clinical trial consortium, funded by the U.S. Department of Defense, that 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.