Neurofibromatosis type 2
Neurofibromatosis type 2
Neurofibromatosis is the general name for a number of genetic conditions that cause tumours to grow along your nerves.
Tumours are abnormal tissue growths. In neurofibromatosis, the tumours are usually non-cancerous (benign).
Neurofibromatosis type 1 (NF1) is the most common type, affecting about 1 in 3,000 births. This is covered separately – read aboutneurofibromatosis type 1.
These pages focus on neurofibromatosis type 2 (NF2) – a less common type, affecting about 1 in 33,000 people.
What are the symptoms of NF2?
Almost everyone with NF2 develops tumours on the nerves responsible for hearing and balance. These typically cause symptoms such as:
gradual hearing loss, that usually gets worse over time
ringing or buzzing in the ears (tinnitus)
balance problems, particularly when moving in the dark or walking on uneven ground
Tumours can also develop inside the brain or spinal cord, or the nerves to the arms and legs. This can cause symptoms such as weakness in the arms and legs, and persistent headaches.
What is the cause?
NF2 is caused by a genetic mutation, which is a permanent change in the DNA sequence that makes up a gene. As a result, the growth of nerve tissue isn't properly controlled.
In half of all cases of NF2, the genetic mutation is passed from a parent to their child. In other cases, the genetic mutation appears to develop spontaneously (sporadic mutation).
Although there are genetic tests that can be carried out during pregnancy to check if your child will have NF2, most cases are diagnosed using tests after birth.
How is it treated?
There's currently no cure for NF2. Treatment involves regular monitoring and treating any problems as they occur.
Surgery can be used to remove most tumours, although it carries a risk of causing problems, such as complete deafness or facial weakness. Therefore, the risks and potential benefits need to be carefully considered before treatment.
Most people with NF2 eventually develop significant hearing loss and often benefit from learning to lip read or using a hearing aid. Special implants can sometimes be inserted to improve a person's hearing.
NF2 tends to get worse over time, although the speed at which this happens can vary considerably. However, most people with NF2 eventually lose their hearing completely, and some people require a wheelchair or other type of mobility device.
Tumours developing inside the brain and spinal cord can place a strain on the body and shorten life expectancy. However, improved techniques used to diagnose, monitor and treat the condition are thought to have increased life expectancy and improved the quality of life for many people with NF2.
The Neuro Foundation
The Neuro Foundation is a UK charity that aims to improve the lives of people with neurofibromatosis (either type 1 or type 2).
Symptoms of neurofibromatosis type 2
Symptoms of neurofibromatosis type 2 (NF2) typically start during the late teens or early twenties, but may develop at any age.
Most of the problems are caused by non-cancerous (benign) tumours, which grow in various part of the body.
Most people with NF2 develop benign tumours in the nerves used by the brain to help with hearing and sense of balance. These are known as vestibular schwannomas.
Vestibular schwannomas can cause ear problems such as:
gradual hearing loss – that usually gets worse over time
a constant ringing or buzzing sound (tinnitus)
balance problems, such as feeling dizzy – this is usually made worse by walking on uneven ground or moving around in the dark
These tumours tend to only cause problems in one ear initially, but both ears are often affected eventually.
Less common symptoms of vestibular schwannomas can include a feeling that your environment is spinning around you (vertigo), nausea and vomiting.
It's likely that these tumours will grow larger over time, eventually causing additional symptoms such as:
numbness in parts of your face
weakness of your tongue – which can cause slurred or unusual-sounding speech and difficulty swallowing (dysphagia)
facial pain – although this is less common
About two-thirds of people with NF2 develop cataracts. These are cloudy patches in the lens (the transparent structure at the front of the eye).
Cataracts can make a person’s vision blurred or misty. However, they're usually mild in NF2 and rarely disrupt vision significantly.
Cataracts are normally associated with old age, but they can develop in children and young adults with NF2.
Just over half of people with NF2 develop benign tumours on or underneath the surface of their skin. These are called schwannomas.
These often take the form of skin plaques. These are small, coloured, raised patches of skin that are usually less than 2cm across.
Tumours that develop under the skin can grow to around the size of a golf ball and they can be painful if they develop along a section of nerves.
Some people with NF2 also develop one or two coffee-coloured patches on their skin, called café au lait spots. However, having lots of café au lait spots is usually a sign of neurofibromatosis type 1 (NF1).
Many people with NF2 will develop a condition called peripheral neuropathy. Peripheral neuropathy is where a section of the nervous system, known as the peripheral nervous system, becomes damaged.
Peripheral neuropathy can cause a wide range of symptoms, depending on which sections of the peripheral nervous system are damaged. Possible symptoms include:
pins and needles in the affected body part
numbness and a reduced ability to feel pain or temperature changes – particularly in your feet
a burning pain – usually in the feet and legs, followed by the hands and arms as the neuropathy progresses
Around half of people with NF2 develop one or more benign tumours inside their brain. These types of tumours are called meningiomas.
Meningiomas may cause no noticeable problems. However, they can sometimes lead to an increase in pressure in and around the brain, causing symptoms such as:
disturbances in vision – such as double vision
The tumours can also disrupt certain brain functions. Depending on where in the brain they're located, this may cause:
weakness or numbness in one side of the body
difficulty speaking, understanding words, writing and reading (aphasia)
fits or blackouts
loss of smell or a sensation of strange smells
unsteadiness, loss of co-ordination and difficulty walking
difficulty speaking and swallowing
Spinal cord problems
Around half of people with NF2 develop one or more benign tumours inside their spinal cord. These are known as ependymomas.
The spinal cord is a long band of nerves that runs from your brain down the centre of the spine.
Around half of people who develop ependymomas won't have any noticeable symptoms. The remaining half may experience:
unpleasant physical sensations in certain parts of the body – such as numbness, tingling, or a "crawling" sensation on the skin
Causes of neurofibromatosis type 2
Neurofibromatosis type 2 (NF2) is caused by a genetic mutation in a gene called NF2.
Genes are the instructions used to produce all human characteristics. A genetic mutation is a permanent change in the DNA sequence that makes up a gene.
Normally, the NF2 gene produces a protein called merlin (also called schwannomin). This protein plays an important role in regulating the growth of nerve tissue.
In someone with NF2, this gene is faulty. This results in the cells producing an incomplete protein, or no protein at all. Without an effective merlin protein, areas of uncontrolled growth (tumours) can develop in the nervous system.
The faulty gene that causes NF2 is found on chromosome number 22.
How it's inherited
In around half of all cases of NF2, the mutated gene is passed down from a parent to their child.
The NF2 mutation is known as an autosomal dominant mutation. This means that only one parent has to have the faulty gene for a child to be at risk of developing the condition.
If either the mother or father has the faulty gene, there's a one in two chance that each child they have will develop NF2.
Males and females have the same chance of developing the condition.
In around half of NF2 cases, the mutation appears to happen spontaneously in either the sperm or egg just before conception. This is known as a sporadic mutation. It's unclear what causes it or whether anything increases the risk of it happening.
If you have a child who develops NF2 as a result of a sporadic mutation, it's highly unlikely that any further children you have will also develop the condition.
A person who develops NF2 sporadically can pass the condition to their children. The chances of this happening are usually the same as those for someone who inherited the condition (see above), unless they develop a form of NF2 called mosaic NF2 (see below).
About one third of people with NF2 just have a mild form of the disease, called mosaic NF2.
Mosaic NF2 develops when the mutation occurs after an embryo has been conceived. This is different from "normal" NF2, where the mutation is already present in the sperm or the egg before conception takes place.
As the mutation takes place later in the development of the embryo, not all the cells of the body are affected in mosaic NF2. Therefore, the symptoms of mosaic NF2 are milder and are often restricted to a certain area or side of the body.
As the genetic mutation isn't in all the cells of someone with mosaic NF2, the risk of having a child with NF2 is less than the usual 50%. However, if the child of someone with mosaic NF2 is affected, they'll have the more common form of the condition.
Diagnosing neurofibromatosis type 2
If someone develops symptoms of neurofibromatosis type 2 (NF2), a number of tests can be used to look for signs of the condition.
A family history of NF2 will also be taken into account when diagnosing the condition.
Some of the tests commonly used to check for signs of NF2 are described below.
A magnetic resonance imaging (MRI) scan uses strong magnetic fields and radio waves to produce detailed scans of the body’s soft tissue. It can be used to check for the presence of non-cancerous (benign) tumours inside the nerve tissue next to your ears, as well as your brain and spinal cord.
Hearing and eye tests
A number of different hearing tests can be used to find out whether your hearing has become impaired.
Eyes tests are often used to check for cataracts (cloudy patches at the front of the eye), which are common in NF2.
A blood test can be used to check your DNA for the NF2 mutation. However, this test only correctly identifies the mutation in about two-thirds of cases, so a negative result doesn't necessarily mean you don't have NF2.
If you or your partner has NF2, there's a chance you could pass it on to any children you have.
You may choose to have treatment to ensure that your children don't develop the condition, or you may wish to have tests during pregnancy to check if your child is affected.
Pre-implantation genetic diagnosis (PGD)
A type of in vitro fertilisation (IVF) treatment called pre-implantation genetic diagnosis (PGD) can be used to help ensure a pregnancy is unaffected by NF2.
In this procedure, several of the woman’s eggs are fertilised by the man’s sperm outside the body to produce embryos. The embryos can then be tested for the NF2 mutation, and one or two healthy embryos will be transferred into the womb.
You may qualify for funding for PGD or you may need to consider paying for this privately. A course of PGD can cost between £6,000 and £10,000, and there's no guarantee that one course of treatment will lead to a successful pregnancy.
Tests during pregnancy
The most commonly used tests to check an embryo for the genetic mutation that causes NF2 include:
chorionic villus sampling (CVS) – where a sample of cells from the placenta are removed and tested, usually between weeks 11 and 14 of pregnancy
amniocentesis – where a sample of amniotic fluid is removed and tested, usually during weeks 15 to 20 of pregnancy
If you wish to have these tests during pregnancy, you'll be referred to a genetic counsellor to discuss the implications of the test result.
If tests show that your child will develop NF2, the genetic counsellor will support you through the testing process and help you decide how you want to proceed with the pregnancy.
Treating neurofibromatosis type 2
Treatment for neurofibromatosis type 2 (NF2) focuses on regular monitoring and, if possible, treating any problems caused by tumours.
Your specialist care team
Because of the rarity of NF2, the has created four specialist centres where healthcare professionals with expertise in treating the condition are based.
The specialist centres are located at:
Guy's and St Thomas' Foundation Trust in London
Addenbrooke's Hospital in Cambridge
Central Manchester University Hospitals
Oxford University Hospitals Trust
If you're diagnosed with NF2, you'll usually be referred to one of these centres so a treatment plan can be drawn up.
Everyone with NF2 requires regular monitoring to check for signs of any problems developing and, if necessary, treatment will be arranged.
Monitoring NF2 usually involves:
annual MRI scans to check whether any new tumours have developed and whether any existing tumours have grown larger
annual eye tests to check for the presence of cataracts (cloudy patches at the front of the eye)
annual hearing tests to check the extent of any hearing impairment
Depending on the extent and severity of your symptoms, more frequent tests may sometimes be required.
Contact your specialist centre if any new symptoms develop in between these examinations, or if any existing symptoms get worse.
The growth of tumours is one of the main problems associated with NF2 and it's not always obvious what the best treatment is.
Many tumours are small and may not grow large enough to cause any problems, but others can be large and have a significant impact on your life.
You should discuss the best option for you with your care team before deciding on a particular treatment.
It's possible to surgically remove some tumours, but the risks involved can often outweigh the benefits.
For example, removing tumours from the nerve tissue next to your ears could further damage your hearing and cause paralysis of your facial muscles.
Removing tumours from the spinal cord carries a small risk of damaging the spinal cord, which could cause some degree of paralysis.
However, in some cases, surgery may be required to prevent potentially serious complications, such as a tumour growing so large that there's a risk of it damaging your brain.
For smaller tumours, a type of radiotherapy known as the gamma knife may be an option. This treatment doesn't involve the use of an actual knife – it uses a tightly focused beam of gamma radiation to shrink a tumour.
As with surgical removal, this treatment carries some risks. There's a possibility that the gamma radiation could cause biological changes to occur in tissue, which could result in any new tumours becoming cancerous. The chances of this happening are thought to be quite small, but it needs to be considered when weighing up your treatment options.
Treating hearing problems
If you have NF2, your hearing will probably become impaired to such an extent that you'll require treatment.
One option may be to consider a hearing implant. These are surgically implanted electrical devices used to bypass problems in the hearing mechanism. There are two types of hearing implants used in NF2, called cochlear implants and auditory brainstem implants (ABIs).
Cochlea implants and ABIs have an external microphone that receives and processes sounds. These signals are passed into an internal receiver before being carried through wires to electrodes either in the cochlea (the coiled, spiral tube inside the inner ear) or the brainstem.
If you have an ABI fitted, the surgeon will first remove any tumours from the hearing nerves. These implants only restore some degree of hearing. However, they can make lip reading easier (see below).
As with all types of surgery, there's a risk of complications. Some of these can be serious, such as infection on the outer layer of the brain (meningitis), which can occur in around 1 in every 60 cases. These risks need to be taken into consideration when deciding the best way to manage your hearing problems.
Another option is learning to lip read. Your treatment centre should be able to recommend a hearing therapist or another healthcare professional who's qualified to teach lip reading.
Treating other problems
NF2 can also cause several other health problems, which require different treatments. For example, NF2 can cause:
childhood cataracts – which is usually treated with surgery to remove the cloudy lens and replace it with a clear artificial lens
peripheral neuropathy – which is usually treated with medication
tinnitus – which may be treated with a number of different therapies, such as tinnitus retraining therapy to help you tune out the constant buzzing or ringing noise