NF2-related schwannomatosis (neurofibromatosis type 2)

Overview

NF2-related schwannomatosis (NF2) is a rare genetic condition. It causes tumors to grow on the hearing and balance nerves, most often in both ears, which can lead to hearing loss. The gene change that causes the tumors can be inherited from a parent. Or the gene change can happen spontaneously. That means it happens for the first time and isn't passed down from a parent.

The condition was previously called neurofibromatosis type 2. The condition itself has not changed — only the name. It causes tumors to grow on the hearing and balance nerves in both ears. These tumors are called vestibular schwannomas. They are not cancer. The tumors can lead to hearing loss or balance problems. People with NF2 also may develop other noncancerous tumors on the brain, spine or nerves. These tumors can include meningiomas, other schwannomas or ependymomas in the spinal cord.

NF2-related schwannomatosis is one type of schwannomatosis, a group of conditions where schwannomas can form in different parts of the body. Schwannomas are noncancerous tumors that start in the cells covering nerves.

NF2 is not cancer. But they can still cause problems by pressing on nearby nerves or the brainstem. Because of this, regular imaging and hearing checks are important. Treatment may include radiation, surgery or targeted medicines such as bevacizumab.

NF2 is rare. It affects about 1 in 60,000 people. Many people have no family history of NF2. Some have mosaic NF2, which means only some cells carry the gene change. This can lead to milder symptoms or symptoms that start later in life.

NF2-related schwannomatosis is different from neurofibromatosis type 1 (NF1). NF1 often begins with skin changes like cafe au lait spots and freckling, and may include neurofibromas, learning differences and optic pathway gliomas. NF2 causes tumors on the hearing and balance nerves that can lead to hearing loss, tinnitus and balance problems, along with other brain or spine tumors. Skin changes in NF2 are usually mild.

Neither type of neurofibromatosis is considered worse. Effects vary from person to person based on which tumors are present, how fast they grow and the symptoms that develop. With careful monitoring, timely treatment and support for hearing and balance, many people live full lives with NF2.

Symptoms

NF2-related schwannomatosis, previously called neurofibromatosis type 2 or NF2, causes symptoms that usually result from slow-growing tumors in both ears. These tumors are known as vestibular schwannomas. They also are called acoustic neuromas. These tumors are benign, which means they are not cancer.

The tumors grow on the nerve that carries sound and balance information from the inner ear to the brain. Because of this, one of the first signs of NF2 is hearing loss in one or both ears. Ringing in the ears and balance problems also are common early symptoms.

While NF2 mostly affects the nerves that control hearing and balance, tumors in other parts of the brain can sometimes affect nearby areas that help with coordination or movement. However, NF2 usually does not directly affect thinking, memory or the hypothalamus, which controls hormones and body functions.

Symptoms often begin in the late teen or early adult years, when tumors start to cause changes in hearing, balance or vision.

Symptoms of NF2 depend on where tumors grow. Common symptoms include:

• Gradual hearing loss.
• Ringing in the ears.
• Poor balance or unsteadiness.
• Headaches.

Some people with NF2 may have small skin lumps or bumps. These are usually caused by tumors growing on nerves under the skin. These lumps and bumps are different from the skin changes seen in other types of neurofibromatosis.

Sometimes NF2 can cause visible changes in the face. Facial muscles may become weak or droop if tumors grow on the facial nerve, which controls movement of the face. This may make it harder to smile, blink or move facial muscles on one side.

NF2 also can lead to the growth of tumors on other nerves, including in the brain, spine and eyes. Tumors also may grow on peripheral nerves, which are outside the brain and spinal cord. People who have NF2 may develop other benign tumors as well.

Symptoms from tumors in other areas may include:

• Numbness and weakness in the arms or legs.
• Pain.
• Poor balance.
• Facial droop.
• Changes in vision or cataracts.
• Seizures.
• Headaches.

Causes

NF2-related schwannomatosis is caused by a change, called an alteration, in the NF2 gene on chromosome 22. This gene makes a protein called merlin. Merlin also is known as schwannomin. It helps control cell growth and prevent tumors. When the gene is altered, the body does not make enough merlin. Without merlin, cells can grow when they should not. This can lead to tumors forming on nerves.

Role of genes and inheritance

For about half of people who have NF2-related schwannomatosis, the altered gene is inherited from a parent. NF2 follows an autosomal dominant inheritance pattern. This means that any child of an affected parent has a 50% chance of having the gene change.

The other half of people with NF2 develop the condition because of a new gene change, called a de novo mutation. This means that neither parent has the gene change. The gene change occurs for the first time in that person.

Mosaic NF2

Sometimes, the gene change occurs in only some of the body's cells. This is called mosaic NF2. People with mosaic NF2 may have milder symptoms or develop them later in life. Because not all cells carry the gene change, the chance of passing NF2 to a child may be lower than 50%.

These gene changes explain why NF2-related schwannomatosis is a condition passed down in families. It is not caused by lifestyle or environmental factors.

Risk factors

For about half of people who have NF2-related schwannomatosis, the altered gene is passed down from a parent. NF2 has an autosomal dominant inheritance pattern. This means any child of an affected parent has a 50% chance of having the gene change. The other half of people with NF2 develop the condition because of a new gene change that was not present in either parent.

Having a family history of NF2 is the only known risk factor. NF2 occurs in people of all backgrounds and regions at similar rates. There are no known geographic or ethnic factors that increase risk.

Complications

NF2 affects many parts of the body because it causes tumors to grow on nerves throughout the brain and spinal cord. NF2 complications vary by which nerves or parts of the brain or spine are involved.

Sensory and communication complications

• Partial or total hearing loss.
• Balance trouble or dizziness.
• Vision changes, including cataracts.
• Speech or swallowing difficulty.

Physical and nerve complications

• Numbness, tingling or weakness in an arm or leg.
• Small skin schwannomas that may cause pain or affect appearance.
• Multiple benign brain or spine tumors that can press on the brain or spinal cord.
• Chronic pain or headaches.

Treatment and emotional complications

• Side effects after treatment, such as hearing decline after surgery or radiosurgery and rare radiation-related tumor effects.
• Emotional stress, anxiety or depression.
• Communication challenges from hearing loss.

How NF2 affects the body beyond hearing loss

NF2 tumors can press on nearby structures in the brain or spinal cord and affect movement, vision, swallowing or balance. Tumors on the spinal nerves can cause numbness, weakness or pain in the arms or legs. Meningiomas may form on the surface of the brain or spine and increase pressure inside the skull, leading to headaches or seizures. Cataracts and other eye problems also are common. Over time, these issues can affect mobility, independence and quality of life. These complications can vary in severity and may change over time.

Because complications can vary, the long-term outlook depends on where and how tumors grow.

Life expectancy with NF2

Life expectancy varies widely. It depends on the number, size and location of tumors. It also depends on how early the condition is diagnosed and treated. Many people with NF2 live into middle or late adulthood, especially with regular monitoring and modern treatments that preserve hearing and nerve function. Advances in MRI techniques, microsurgery and targeted medicines have improved outcomes and helped people maintain a longer, higher quality life.

NF2 is not cancer. But its tumors can cause serious complications if they press on vital areas of the brain or spinal cord. These problems can be life-threatening in some cases, especially without monitoring or treatment.

Recurrence or regrowth of tumors

NF2-related tumors, especially vestibular schwannomas and meningiomas, can grow back after surgery. Complete removal can be difficult if tumors are close to vital nerves or brain structures. Even after successful surgery, new tumors may appear in other areas over time because the underlying genetic change remains in the body's cells. Ongoing MRI scans, hearing tests and neurological exams are important to find and manage new or recurrent growth early.

Diagnosis

Diagnosis and tests

NF2-related schwannomatosis (NF2) is diagnosed through a mix of hearing tests, imaging and genetic testing. Most people are diagnosed when they have hearing loss, ringing in the ears or balance trouble. These are often the first signs of tumors called vestibular schwannomas. They grow on the nerves that connect the inner ear to the brain.

Early detection through hearing tests, MRI and genetic testing helps guide treatment and preserve hearing.

Medical history and exam

A detailed history and physical exam help find early signs of NF2 complications, such as hearing loss, balance changes or muscle weakness. An eye exam can detect cataracts or changes to the optic nerve.

Hearing and balance tests

Other tests, such as auditory brainstem response (ABR) and vestibular testing, show whether the hearing and balance nerves are sending signals properly. Unusual results can be another clue that vestibular schwannomas are present and help confirm an NF2 diagnosis.

Imaging tests

Brain MRI is the key test for diagnosing NF2. It can find vestibular schwannomas on the hearing and balance nerves. Spine MRI helps find tumors in the spinal cord such as schwannomas and ependymomas. MRI may find tumors before symptoms appear. Follow-up MRI and hearing tests track growth and guide care.

Genetic testing

Genetic testing looks for a change in the NF2 gene. Finding this change can confirm NF2. A blood test can find a gene change you were born with, whether it was inherited from a parent or happened spontaneously for the first time.

Sometimes the blood test is negative even when NF2 is likely. In that case, testing the tumor can find the change and show mosaic NF2, which means only some cells have the gene change.

Diagnosis in children and families

If a parent has NF2, children can be tested. Genetic counseling can help families understand the risks and timing of screening. Early MRI and hearing tests help catch tumors when treatment can best protect hearing and nerve function.

Treatment

There is no cure for NF2-related schwannomatosis (NF2). But treatment can help manage tumors and protect hearing, balance and nerve function. The goal of treatment is to control tumor growth, relieve symptoms and maintain quality of life for as long as possible.

Care is often provided by a team that includes specialists in neurology, neurosurgery, ear care and hearing, eye care, and rehabilitation. Regular MRI scans and hearing tests are used to monitor tumor size and function over time.

Surgery

Surgery may be recommended for tumors that grow quickly, cause pain, or affect hearing or balance. The goal is to remove as much tumor as possible while protecting nearby nerves. For vestibular schwannomas — tumors on the hearing and balance nerves — surgery to save hearing may be possible when the tumor is small.

Sometimes, surgeons may remove the tumor completely to relieve pressure on the brain or spinal cord. Because NF2 tumors often occur in multiple places, each surgery is planned individually to lower the chance of nerve injury and hearing loss.

Radiation therapy

Stereotactic radiosurgery may be used for smaller tumors or when surgery is not possible. This treatment uses precisely targeted radiation to stop or slow tumor growth. However, radiation carries some risk of nerve damage or new tumor growth later in life, so it is used carefully.

Targeted therapy

Targeted medicines work on a specific pathway inside the tumor. They are designed to block the signals that help the tumor grow. One of these medicines, bevacizumab, blocks blood vessel growth. It has shown benefit for some people with growing vestibular schwannomas. In studies, it reduced tumor size and helped preserve hearing for many people.

Hearing and rehabilitation

When hearing is lost, auditory implants can help restore sound awareness. Options include cochlear implants if the cochlear nerve is still working, or auditory brainstem implants when both hearing nerves are damaged. A cochlear implant sends sound signals directly to the hearing nerve inside the inner ear. A brainstem implant bypasses the ear entirely and sends sound signals straight to the brain.

Physical therapy, balance training and vision care also can improve daily function and safety.

Ongoing monitoring

Because NF2 can cause new tumors over time, lifelong follow-up is important. MRI scans, hearing and eye exams, and physical evaluations help guide when and how to treat. Regular visits at a center experienced in neurofibromatosis allow early detection of changes and help maintain quality of life.

Other targeted medicines and combination approaches are being studied in clinical trials.

Potential future treatments

Researchers are studying new medicines and approaches to slow tumor growth and help preserve hearing for people with NF2-related schwannomatosis. Many of these options are available only in clinical trials at centers with neurofibromatosis expertise.

Other targeted drugs, such as everolimus, erlotinib and lapatinib, are being studied for NF2 but are not yet proved or approved to treat NF2. Early studies look at whether these medicines can shrink tumors or stabilize hearing.

Research also is exploring newer medicines that act on tumor-growth pathways, including VEGF, mTOR and MAPK. These treatments aim to slow growth or reduce tumor size, but they remain experimental.

Researchers are evaluating how to use bevacizumab most effectively, including dosing and maintenance strategies. They also are looking at whether combining targeted drugs or pairing them with other treatments may improve results. These approaches are still under study.

These studies are part of a growing effort to find targeted therapies for NF2-related schwannomatosis that control tumors while protecting hearing and nerve function.

If you are interested in newer options, your care team may discuss clinical trials to see whether any are a good match for your situation and goals.

Coping and support

Learning you have NF2 can cause many feelings. Staying connected helps. A support group, counseling and talking with people you trust can lower stress and make day-to-day life easier.

Ways to cope day to day

• Hearing support. Consider using hearing aids or cochlear or auditory brainstem implants. Captioned phone and video also may help.
• Balance and safety. Vestibular rehabilitation therapy, regular exercise and simple steps to prevent falls at home can help you cope with these issues.
• Communication tools. Consider speech-to-text apps and alerting devices for phones and doorbells.
• Pain and headaches. Ask your care team about medicines, physical therapy and relaxation skills.
• Emotional health. Counseling, cognitive behavioral therapy and peer support can help you learn to manage stress and other feelings.
• School or work. Ask for accommodations such as captioning, quiet spaces, flexible schedules and written instructions.
• Follow-up care. Get regular hearing tests and MRI scans to catch changes early. These steps can improve daily function and quality of life.

Finding support

Getting help from people and programs can make daily life easier and less stressful. Support may be available from:

• National neurofibromatosis groups and local chapters.
• Hospital-based neurofibromatosis clinics and social work services.
• Online NF2 communities and moderated forums.
• Family, friends and caregivers.
• Genetic counseling for family planning and testing.

These supports can help you feel informed, connected and in control.

Neurofibromatosis clinics often include social workers or psychologists who can help coordinate care and connect you to community programs.

Preparing for an appointment

You may be referred to a specialist in brain and nervous system conditions, known as a neurologist.

Here's some information to help you get ready for your appointment.

What you can do

When you make the appointment, ask if there's anything you need to do in advance, such as fasting before a specific test. Before your appointment:

• Write down a list of concerns, making a note of when you first noticed them.
• Bring a complete medical and family history with you.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medicines, vitamins or supplements that you are taking.
• Write down questions to ask your healthcare professional.

Treatment

For NF2, basic questions to ask include:

• What tests do I need?
• What treatments are available?
• How should the condition be monitored for changes?

Don't hesitate to ask other questions.

Preparing for an appointment

What to expect from your doctor

Your healthcare professional is likely to ask you several questions. They may include:

• When did you first notice symptoms?
• Have your symptoms changed over time?
• Is there a family history of NF2?