Neurofibromatosis type 1
Neurofibromatosis is the general name for a number of genetic conditions that cause tumours to grow along your nerves.
Tumours are swellings formed by a growth of cells. In neurofibromatosis, the tumours are usually non-cancerous (benign).
Neurofibromatosis type 1 (NF1) is the most common type, affecting about one in 3,000 births.
Neurofibromatosis type 2 (NF2), which is much less common, has different symptoms and is caused by changes in different genes, so is covered separately.
What are the symptoms of NF1?
NF1 is a condition you're born with, although some symptoms develop gradually over many years. The severity of the condition can vary considerably from person to person.
In most cases of NF1 the skin is affected, causing symptoms such as:
pale, coffee-coloured patches (café au lait spots)
soft, non-cancerous bumps on or under the skin (neurofibromas)
Certain health problems are often associated with NF1, such as learning difficulties. Less commonly, NF1 is associated with a type ofcancer known as malignant peripheral nerve sheath tumours.
What is the cause?
NF1 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 NF1, the genetic mutation is passed from a parent to their child. In other cases, the genetic mutation appears to develop spontaneously.
Although genetic tests can be carried out during pregnancy to check if your child will have NF1, most cases are diagnosed after birth from the characteristic symptoms.
How is it treated?
There's currently no cure for NF1. Treatment involves regular monitoring and treating any problems as they occur.
This can involve surgery to remove tumours and improve bone abnormalities, medication to control secondary conditions such as high blood pressure, and therapy for behavioural problems.
In many cases, careful monitoring and treatment can help people with NF1 live a full life. However, there's a risk of developing serious problems such as certain types of cancer, which can reduce life expectancy in some people by up to 15 years.
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 1
For many people with neurofibromatosis type 1 (NF1), the condition is mild and causes no serious health problems. But some people will have severe symptoms.
NF1 can affect several areas of the body, but it's unlikely someone with the condition will develop all the symptoms below.
The most common symptom of NF1 is the appearance of painless coffee-coloured patches on the skin, known as café au lait spots. They affect 95% of people with NF1. The spots can be present at birth or develop by the time a child is three years old.
During childhood, most children with NF1 will have at least six café au lait spots around 5mm across. These grow to about 15mm during adulthood.
The number of café au lait spots someone has isn't related to the severity of the condition. For example, a person with 10 spots has the same chance of developing further problems as someone with 100 spots.
Having a couple of café au lait spots doesn't necessarily mean you have NF1. About one in 10 people without the condition have one or two of these spots.
Another common symptom of NF1 is clusters of freckles in unusual places, such as the armpits, groin and under the breast.
Bumps on or under the skin
As a child gets older, usually during teenage years or early adulthood, they develop bumps on or under their skin (neurofibromas). These are caused by non-cancerous tumours that develop on the coverings of nerves. They may vary in size, from pea-sized to slightly bigger tumours. Some neurofibromas have a purple colour.
The number of neurofibromas a person has can vary. Some people only have a small number while others have them on large sections of their body.
Most neurofibromas aren't particularly painful, but may look unattractive, catch on clothes and occasionally cause irritation and stinging.
However, if neurofibromas develop where multiple branches of nerves come together (plexiform neurofibromas), they can cause large swellings. Plexiform neurofibromas sometimes occur on the skin, but may also develop on larger nerves deeper in the body. They may sometimes cause symptoms including pain, weakness, numbness, bleeding, or bladder or bowel changes.
Learning and behaviour
Some children with NF1 develop learning and behavioural problems. It's unclear why this happens. Around 60% of children with NF1 have a learning difficulty, which is usually mild.
One way of measuring intelligence is using a scoring system known as an intelligence quotient (IQ). Average intelligence is set at an IQ of 100.
Children with NF1 who have a learning difficulty may have normal or slightly lower than average intelligence. Most children with NF1 can be taught at a mainstream school. They may have specific learning problems such as difficulty with reading, writing, maths and co-ordination.
The behavioural condition attention deficit hyperactivity disorder (ADHD) affects around half of all children with NF1. Children with ADHD have problems with attention span, concentration and controlling impulses. NF1 has also been linked with autism spectrum disorder (ASD) and some children may have difficulty in social communication.
Around 15% of children with NF1 develop a tumour on their optic pathway. The optic pathway is located at the back of each eye and sends information from the eyes to the brain. This type of tumour is known as an optic pathway glioma (OPG).
Children under seven years of age are known to have the highest risk of developing this type of tumour. Many are small, grow slowly and don't cause any noticeable symptoms. Children with faster-growing OPGs may have problems with their vision, including:
objects becoming blurry
changes in how they see colours
a reduced field of vision
one eye looks more prominent than the other
Younger children may be unable to explain that they have vision problems. You should be aware of any indications your child has difficulty seeing, such as problems picking up small objects or bumping into things. The best way of detecting these tumours is to have eye tests at least every year until your child is at least seven years old.
Another common feature of NF1 is the appearance of tiny brown spots in the iris (the coloured, central part of the eye). These are known as Lisch nodules and don't usually cause any noticeable symptoms or vision problems.
High blood pressure
Some children with NF1 develop high blood pressure. This is thought to be because the normal workings of the kidneys are affected by narrowing of the arteries. The kidneys help keep blood pressure at a healthy level.
In rare cases, high blood pressure may be caused by a tumour called a phaeochromocytoma. This causes a release of certain hormones, such as adrenaline, which raise blood pressure.
High blood pressure may be associated with potentially serious complications, such as a stroke or a heart attack, if it's not treated. Children and adults with NF1 are recommended to have regular blood pressure checks, usually at least once a year.
Many children with NF1 have one or more problems affecting their physical development. These can include:
a curved spine (scoliosis) – thought to affect around 10% of children with NF1
a larger than average head – this occurs in around half of all children
smaller size and weight than normal – this is common in many people with NF1
Around 2% of children with NF1 develop pseudarthrosis. This is when abnormal bone development leads to a minor bone fracture, usually in the bone of the lower leg (the tibia). In rare cases, the condition can affect long bones in the arm (ulnar or radius).
The fracture doesn't heal completely, which affects the normal movement of the leg. This usually causes it to curve, known as leg bowing.
Some people with NF1 have very low levels of vitamin D. Vitamin D is needed to keep the bones strong. Vitamin D comes from sunlight and may be found in milk, cheese, yoghurt and oily fish.
The brain and nervous system
Symptoms affecting the brain and nervous system are relatively common in NF1.
Many people with NF1 experience migraines, although they're not specific to NF1 and are common in people who don't have the condition.
Around 5% of people develop brain tumours. The tumours may cause no noticeable symptoms. However, tumours in certain parts of the brain occasionally cause symptoms, such as:
weakness on one side of the body
difficulties with balance and co-ordination
Around 7% of children with NF1 develop epilepsy, where a person has repeated seizures or fits. This tends to be a mild form of epilepsy that's controlled easily with medication.
Malignant peripheral nerve sheath tumour
One of the most serious problems that can affect a person with NF1 is a malignant peripheral nerve sheath tumour (MPNST).
MPNSTs are a type of cancer that develops within a plexiform neurofibroma (see above). It's estimated that people with NF1 have a 10% chance over their lifetime of developing a MPNST. Most cases first develop when people are in their late twenties or early thirties, but can occur at any age.
Symptoms of an MPNST include:
the texture of an existing neurofibroma changing from soft to hard
an existing neurofibroma suddenly growing much larger
persistent pain lasting for more than a month or waking you up at night
suddenly having problems with your nervous system that you didn't have before, such as weakness, numbness or tingling in your arms and legs
loss of bladder or bowel control
difficulty with breathing or swallowing
If you have any of these symptoms, contact the doctor in charge of your care as soon as possible.
You should be referred to a specialist centre with experience in diagnosing and treating MPNST.
There are currently two such centres, one in Guy’s & St ThomasFoundation Trust in London and the other in the Central Manchester University Hospitals Foundation Trust.
NF1 and pregnancy
Most women with NF1 have healthy pregnancies.
However, the number of neurofibromas may increase because of hormone changes. Make sure you're cared for by an obstetrician with knowledge of NF1, or speak to your NF1 specialist.
Causes of neurofibromatosis type 1
Neurofibromatosis type 1 (NF1) is caused by a genetic mutation in a gene called NF1.
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 NF1 gene is responsible for producing a protein that helps regulate the growth of nerve tissue. The protein "switches off" the growth of tissue once it's reached a certain size.
In someone with NF1, this gene is faulty. This leads to the cells producing an incomplete protein that's much less effective at switching off the growth of nerve tissue, leading to uncontrolled growth (tumours) developing in the nervous system.
The faulty gene that causes NF1 is found on chromosome number 17.
How it's inherited
In around half of all cases of NF1, the mutated gene is passed down from a parent to their child.
The NF1 mutation is known as an autosomal dominant mutation. This means 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 each child they have will develop NF1. Males and females have the same chance of developing the condition.
The severity of the condition isn't always inherited. For example, a child may have mild NF1 even if they inherited the condition from one of their parents who's more severely affected.
In around half of NF1 cases, the mutation appears to happen spontaneously in either the sperm or egg just before conception (sporadic mutation). It's unclear what causes it or whether anything increases the risk of it happening.
If you have a child who develops NF1 as a result of a spontaneous mutation, it's highly unlikely any further children you have will also develop the condition.
A person who develops NF1 sporadically can pass the condition to their children. The chances of this happening are the same as for someone who inherited the condition themselves (see above).
Diagnosing neurofibromatosis type 1
Neurofibromatosis type 1 (NF1) is usually diagnosed by checking for the characteristic symptoms of the condition.
A confident diagnosis can usually be made if two or more of the following symptoms are present:
six or more café au lait spots (coffee-coloured skin patches) larger than 5mm in children, or 15mm in adults
freckles under the arms or around the groin
two or more neurofibromas (bumps on or under the skin), or one plexiform neurofibroma (a neurofibroma that develops where multiple branches of nerves come together)
a tumour on the optic nerve (an optic glioma), which rarely causes symptoms or affects sight
two or more tiny brown spots in the iris (the coloured part of the eye), known as Lisch nodules
bone defects, such as bowing of the lower leg
a family history of NF1
It's usually easy to diagnose NF1 in adults and older children, but it can take several years for all the symptoms to develop in young children. As a result, it's not always possible to make a firm diagnosis before a child is five years old.
Further tests may be recommended to assess whether your child has developed additional symptoms or secondary conditions known to be associated with NF1. Some of these tests are described below:
X-rays can check for any problems with the normal development of the bones.
An MRI can produce more detailed images of the soft tissue of the body and check for non-cancerous tumours along the optic pathway, brain and nervous system. They can also detect deep internal neurofibromas.
A simple blood pressure test is often used to measure your child’s blood pressure.
A biopsy, where a small tissue sample is removed from the body for further testing, can be used to check for cancerous cells. This is only done in specialist centres.
An electroencephalogram (EEG), which measures electrical activity in the brain, can be used if your child has had seizures (fits).
If there's uncertainty about the diagnosis, your child can be tested to see whether they have the NF1 mutated gene. This involves extracting DNA from a sample of their blood and analysing it to check whether they've inherited the faulty gene.
However, the test isn't always completely reliable. Around 5% of children who test negative for the mutated gene still develop NF1.
Before and during pregnancy
Couples with a family history of NF1 who are thinking of having a baby can be referred to a genetics specialist for advice.
A genetic counsellor can help couples work through the decision-making process and explain possible alternatives, such as adoption or artificial insemination (where sperm taken from the man is inserted directly into his partner’s womb).
There are also a number of tests that can be carried out during pregnancy to check if a baby will develop NF1. These include:
chorionic villus sampling (CVS) – where a small sample of placenta is removed from the womb and tested for the NF1 gene, usually during weeks 11 to 14 of pregnancy
amniocentesis – where a sample of amniotic fluid is taken for testing, usually during weeks 15 to 20 of pregnancy
However, these tests can't determine how severe the condition will be. Even if a parent is severely affected by the condition, it doesn't mean their children will be.
Pre-implantation genetic diagnosis
For couples at risk of having a child with NF1, pre-implantation genetic diagnosis (PGD) may be an option.
PGD involves using in-vitro fertilisation (IVF), where eggs are removed from a woman's ovaries before being fertilised with sperm in a laboratory. After a few days, the resulting embryos can be tested for NF1 and a maximum of two unaffected embryos are transferred into the uterus.
However, funding for PGD is decided on an individual basis. For example, you may be considered ineligible for PGD on the if you already have unaffected children or if the chances of success are thought to be low. In these cases you can choose to fund PGD yourself, although it's likely to cost between £6,000 and £10,000.
Treating neurofibromatosis type 1
Someone with neurofibromatosis type 1 (NF1) will need regular monitoring and any problems treating by a team of health professionals.
If you develop complex problems, you'll usually be referred to one of two specialist centres so a treatment plan can be drawn up. These are:
Guy’s & St Thomas’ Foundation Trust in London
Central Manchester University Hospitals Foundation Trust
Most children with NF1 are recommended to have a comprehensive examination each year. This may include:
a detailed examination of their skin to check for new neurofibromas (bumps on or under the skin) or changes in existing ones
a vision test and an examination of both eyes
a bone assessment to check for problems such as scoliosis(abnormal curvature of the spine) or poorly healed bone fractures
a blood pressure measurement
measuring your child’s physical development
assessing your child’s progress at school – abilities in activities such as reading, writing, problem solving and comprehension
As a child gets older, they should ideally still be seen once a year. Over time they'll learn to monitor their own health so they know when to seek help. However, they may need more assessments if they develop complex health needs.
Contact your specialist centre if your child develops any new symptoms in between their annual examinations, or if their existing symptoms get worse.
Café au lait spots
Usually, there's no need for treatment of café au lait spots, which are common in NF1. Sometimes they fade as people get older. Laser treatment is not helpful if you have a lot of them.
If your child finds these patches particularly distressing, one option is to use make-up to cover them up. Camouflage make-up specially designed for covering up skin blemishes is available over the counter at pharmacies.
The bumps on or under the skin (neurofibromas) may not require any treatment if they're small. However, treatment can be used if the neurofibromas:
are particularly unsightly and cause emotional distress
cause irritation, itchiness or pain
In most cases, plastic surgery is required. The surgeon cuts the neurofibromas out of the body before resealing the skin. Some small neurofibromas can be treated using laser surgery.
The results of surgery are usually good and most people who have had surgery are happy with the results, although the procedure can leave some thickened scarring and occasionally there may be a delay in wound healing.
Surgery for plexiform neurofibromas (painful neurofibromas that develop inside branches of nerves) can be more challenging. This is because these types of tumours often spread into nearby tissue and may press on important bone structures.
Damage to the nerves can sometimes occur after surgery. This can lead to complications such as a loss of sensation or an inability to move a part of the body. One small study that looked at 120 people who had surgery for plexiform neurofibromas found that around 5% of them had nerve damage.
You should consult a specialist neurofibromatosis centre for advice about removal of plexiform neurofibromas.
If your child has a learning difficulty, your local authority should draw up a Statement of Special Educational Needs. The statement outlines your child’s special educational needs and how they can be met. For example, a statement may set out how many hours of teaching support your child should get each week. The statement will be reviewed every year.
As well as extra teaching, some children with NF1 require additional support from other professionals, such as:
a speech and language therapist
an educational psychologist, who helps improve the person's learning abilities
an occupational therapist, who helps improve the person's skills needed to carry out daily activities
Behavioural conditions, such as attention deficit hyperactivity disorder (ADHD), are usually treated using a combination of:
medications, such as methylphenidate, to help improve attention span and concentration
therapy, such as psychotherapy, where your child will be encouraged to discuss how ADHD affects them and how they could find better ways of coping with the condition
If your child has a social communication disorder, they should be referred to a specialist psychologist for assessment.
High blood pressure
Some people can control high blood pressure by making lifestyle changes including:
reducing the amount of salt in your diet
doing regular exercise
maintaining a healthy weight
not smoking and moderating alcohol consumption (in adults)
Very high blood pressure requires treatment with medication.
Optic nerve tumours
If your child develops a tumour inside the nerve connecting the eye and the brain (the optic nerve) and it doesn't cause any symptoms, no immediate treatment is necessary. This type of tumour, known as an optic pathway glioma (OPG), is usually very small and slow growing.
However, if your child has an OPG, they will need regular eye examinations so the status of the tumour can be closely monitored. If your child experiences symptoms, chemotherapy can be used to help shrink the tumour.
If your child develops an abnormally curved spine (scoliosis), treatment depends on how severe the curvature is.
Mild cases don't always require treatment because your child’s spine may correct itself as they get older. Moderate cases can be treated using a back brace. This device is worn by your child and is designed to correct the position of their spine over time.
Surgery may be required for severe cases of scoliosis to realign the bones of the spine into the correct position.
Surgery can also be used to treat poorly healed bone fractures that disrupt the normal movement of the bones (known as pseudarthrosis).
Possible surgical options are to reconnect two pieces of bone using metal screws and rods or to carry out a bone graft. A bone graft is where a fracture in the bone is repaired by taking a small section of bone from another part of the body and using it to "plug" the fracture. The grafted section of bone will grow into the surrounding bones.
In a small number of cases involving the bones of the limbs, surgery doesn't repair the bone. In this case, it's necessary to amputate a section of the limb in order to restore normal function.
People with pseudarthrosis should always be referred to specialist orthopaedic centres used to treat this complication.
Brain and nervous system problems
Tumours developing inside the brain or nervous system don't always cause symptoms, but can disrupt the normal functions of the body.
If treatment is needed, it may involve surgery, drug treatment, or in some cases radiotherapy (where doses of high-energy waves are used to kill cells).
However, radiotherapy can increase the risk of someone with NF1 developing cancer. Therefore, this treatment should only be used if absolutely necessary and after consultation with doctors experienced in treating NF1.
Epilepsy can be treated with a number of different medications that help reduce the frequency of seizures.
Malignant peripheral nerve sheath tumour
If you develop cancer in a neurofibroma on the nerve covering (known as malignant peripheral nerve sheath tumour or MPNST), surgically removing the tumour is usually recommended.
Radiotherapy and chemotherapy may be given after surgery to reduce the risk of the cancer coming back, although there are some uncertainties about how effective these additional treatments are.
Glomus tumours are benign tumours that form around the nail bed in the fingers or toes. Sometimes they lead to purple discolouration around the nail bed.
People with glomus tumours may experience severe pain in a finger after knocking it, when there is change in temperature or if they press on the nail bed.
Glomus tumours are sometimes diagnosed with an MRI scan. They can be removed surgically and this cures the symptoms.