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Neurofibromatosis type 1



NHS Choices Syndication

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Neurofibromatosis type 1

Causes of neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is caused by a genetic mutation in a gene called the NF1 gene.

Genes are the instructions that are used to produce all human characteristics.

The NF1 gene is responsible for producing a protein that helps regulate the growth of nerve tissue. The protein effectively “switches off” the growth of tissue once it has reached a certain size.

However, the mutation causes some of the instructions inside the body’s cells to become scrambled. This leads to the cells producing an incomplete protein that is much less effective at switching off the growth of nerve tissue, leading to multiple areas of 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 is a one in two chance each child that they have will develop NF1. Males and females have the same chance of developing the condition.

The severity of the condition is not always inherited. For example, a child may have mild NF1 even if they inherited the condition from one of their parents who is more severely affected.

Sporadic mutation

In around half of NF1 cases, the mutation appears to occur in either the sperm or egg just before conception. This is known as a sporadic mutation. It is 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 sporadic mutation, it is 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).

Read more about genetics.

Published Date
2013-08-27 16:20:12Z
Last Review Date
2013-04-15 00:00:00Z
Next Review Date
2015-04-15 00:00:00Z
Classification
Neurofibromatosis


NHS Choices Syndication

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Neurofibromatosis type 1

Complications of neurofibromatosis type 1

Living with any long-term condition can be stressful and upsetting, especially conditions such as neurofibromatosis type 1 (NF1) that affect physical appearance.

Even people with mild cases of NF1, where the appearance of the skin is relatively unchanged, can feel self-conscious about their appearance.

Feelings of stress and self-consciousness can trigger episodes of depression and anxiety, particularly as a child with NF1 gets older and becomes more aware of their appearance.

Signs that your child may be depressed or anxious include:

  • performing poorly at school
  • a loss of interest in activities they used to enjoy
  • no longer socialising with friends

If you are concerned about your child, encourage them to talk about their feelings to determine whether they need additional support and treatment.

It is recommended that adults with NF1 who have feelings of depression and anxiety should contact their GP for advice.

For more information, see is your child depressed? and tips for coping with depression.

Support groups

There are several organisations and support groups for both children and adults with NF1. They offer services such as helplines and online forums and blogs written by people with the condition.

These organisations include:

Published Date
2013-08-27 17:23:57Z
Last Review Date
2013-04-15 00:00:00Z
Next Review Date
2015-04-15 00:00:00Z
Classification
Brain,Brain tumours,Brain tumours (benign),Cancer and tumours,Epilepsy,Eye,Memory problems,Nerves,Neurofibromatosis,Scoliosis,Skin,Skin tumours,Speech problems


NHS Choices Syndication

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Neurofibromatosis type 1

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) that are 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). These are known as Lisch nodules 
  • bone defects, such as bowing of the lower leg
  • a family history of NF1

It is 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 testing

Further tests may be recommended to assess whether your child has developed additional symptoms or secondary conditions that are 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 will often be 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).

Genetic testing

If there is 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 have inherited the faulty gene.

However, the test is not 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 10 to 13 of pregnancy
  • amniocentesis – where a sample of amniotic fluid is taken for testing, usually during weeks 15 to 20 of pregnancy

However, these tests cannot determine how severe the condition will be. Even if a parent is severely affected by the condition, it does not 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 NHS 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 is likely to cost between £6,000 and £10,000.

Published Date
2013-08-27 16:40:01Z
Last Review Date
2013-04-15 00:00:00Z
Next Review Date
2015-04-15 00:00:00Z
Classification
Brain tumours,Counselling,Neurofibromatosis


NHS Choices Syndication

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Neurofibromatosis type 1

Introduction

Neurofibromatosis is the 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).

Types of neurofibromatosis

There are two main types of neurofibromatosis:

  • Neurofibromatosis type 1 (NF1) is the most common type of neurofibromatosis, affecting about one in 3,000 births.
  • Neurofibromatosis type 2 (NF2) is a less common type of neurofibromatosis, affecting about one in 35,000 births.

Despite sharing the same name, these two types of neurofibromatosis are separate conditions with different symptoms and caused by changes in different genes.

This information is about neurofibromatosis type 1 (NF1).

Find out more about neurofibromatosis type 2.

How it affects you

NF1 is a condition you are 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 with smooth outlines (café au lait spots)
  • soft, non-cancerous bumps on or under the skin (neurofibromas)

About one in three people with NF1 also develop a range of further health problems, including:

  • high blood pressure
  • a curved spine (scoliosis)
  • learning difficulties and behavioural problems
  • a type of cancer known as malignant peripheral nerve sheath tumours, which affects around 10% of people with NF1 over their lifetime

Read more about the symptoms of neurofibromatosis type 1 and the complications of neurofibromatosis type 1.

Why it happens

NF1 is caused by a genetic mutation. This is where the instructions that are carried in all living cells become scrambled in some way. As a result, the growth of nerve tissue is not controlled properly.

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 on its own. This is known as a sporadic mutation.

Although there are genetic tests that can be carried out during pregnancy to check if your child will have NF1, most cases are diagnosed after birth from the characteristic symptoms.

Read more about the causes of neurofibromatosis type 1 and diagnosing neurofibromatosis type 1.

How it’s treated

There is currently no cure for NF1. Instead, people with the condition are regularly monitored for further problems and treated if and when these develop.

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 is a risk of developing serious problems such as strokes and some types of cancer, which can reduce life expectancy in some people by up to 15 years.

Read more about treating neurofibromatosis type 1.

Published Date
2013-12-11 12:41:12Z
Last Review Date
2013-04-15 00:00:00Z
Next Review Date
2015-04-15 00:00:00Z
Classification
Neurofibromatosis


NHS Choices Syndication

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Neurofibromatosis type 1

Symptoms and features of neurofibromatosis type 1

The severity of neurofibromatosis type 1 (NF1) can vary considerably. For many the condition is mild and causes no serious health problems, but for others the condition can be severe.

NF1 can affect several areas of the body, although it is unlikely someone with the condition will develop all the symptoms below.

The skin

Coffee-coloured patches

The most common symptom of NF1 is the appearance of multiple, 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 will then grow to about 15mm during adulthood.

The number of café au lait spots someone has is not 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 does not necessarily mean you have NF1. About one in 10 people without the condition have one or two of these spots.

Freckles

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 will develop bumps on or under their skin. These are known as neurofibromas. They are caused by multiple, non-cancerous tumours that develop on the surface of nerve tissue beneath the skin. They are usually pea-sized during childhood and get larger as a person gets older.

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 are not particularly painful, but they can 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, painful swellings. Plexiform neurofibromas may sometimes occur on the skin, but may also develop on the large nerves deeper within the body.

Learning and behaviour

Some children with NF1 develop learning and behavioural problems. It is 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 a 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) is also relatively common and affects around half of all children with NF1. Children with ADHD have problems with attention span, concentration and controlling impulses.

The eyes

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 do not 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
  • squinting

Younger children may be unable to explain that they have vision problems. Therefore, you should be aware of any indications that 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 symptom is the appearance of tiny brown spots in the iris (the coloured, central part of the eye). These are known as Lisch nodules and do not usually cause any noticeable symptoms or vision problems.

High blood pressure

It is estimated that around 20% of children with NF1 will develop high blood pressure. This is thought to be because tumours disrupt the normal workings of the kidneys, which help keep blood pressure at a healthy level.

High blood pressure may be associated with potentially serious complications, such as a stroke or a heart attack if it is not treated. Due to this risk, it is recommended that children and adults with NF1 have regular blood pressure checks, usually at least once a year.

Physical development

Many children with NF1 have one or more problems that affect their physical development. These can include:

  • a curved spine – this is called scoliosis and is thought to affect around 10% of children with NF1
  • a larger than average head – this occurs in around half of all cases
  • smaller size and weight than normal – this is common in most cases of 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).

The fracture does not heal completely, which affects the normal movement of the leg. This usually causes it to curve, which is 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 that affect the brain and nervous system are relatively common in NF1.

Many people with NF1 experience migraines, although they are not specific to NF1 and are common in people who do not 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:

  • personality changes
  • 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 is 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 is estimated that people with NF1 have a 10% chance over their lifetime of developing a MPNST. Most cases first develop between the ages of 20 and 35.

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 that lasts for more than a month or wakes you up at night
  • suddenly having problems with your nervous system that you did not have before, such as weakness, numbness or tingling in your arms and legs
  • loss of bladder or bowel control

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 Thomas’ NHS Foundation Trust in London and the other in the Central Manchester University Hospitals. 

Published Date
2013-08-27 16:15:41Z
Last Review Date
2013-04-15 00:00:00Z
Next Review Date
2015-04-15 00:00:00Z
Classification
Birthmarks,Cataracts,Hearing loss,Neurofibromatosis


NHS Choices Syndication

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Neurofibromatosis type 1

Treating neurofibromatosis type 1

There is currently no cure for neurofibromatosis type 1 (NF1), so management involves regular monitoring and treatment for problems as and when they arise.

As NF1 is a relatively rare condition, it’s likely your care will be managed by a team of health professionals working at a specialist centre.

Monitoring

It’s recommended that most children with NF1 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 test
  • measuring your child’s physical development
  • assessing your child’s abilities in activities such as reading, writing, problem solving and comprehension

As a child gets older, they may have fewer examinations if their symptoms are mild. However, they may need more examinations 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.

Skin problems

Café au lait spots

There is currently little effective treatment for coffee-coloured patches (café au lait spots), which are common in NF1. Laser treatment has been tried with little effect.

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.

Neurofibromas

The bumps on or under the skin (neurofibromas) may not require any treatment if they are small. However, treatment can be used if the neurofibromas:

  • are particularly unsightly and cause emotional distress
  • cause irritation, itchiness or pain
  • press on vital structures of the body, such as the hands, feet or eyes

It may be possible to remove small neurofibromas using laser surgery. However, in most cases, plastic surgery is required. The surgeon will cut the neurofibromas out of the body before resealing the skin.

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 scarring and occasionally there may be a delay in wound healing.

Plexiform neurofibromas

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 bone.

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 (paralysis). 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.

Learning difficulties

If your child has a learning difficulty, your local authority should draw up a Statement of Special Educational Needs (SEN). The statement will outline what your child’s special educational needs are and how they can be met. For example, a SEN may state how many hours of teaching support your child should get each week. The SEN 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, who is trained to help people who have problems with any aspect of speech and language
  • an educational psychologist, who helps people who have problems adapting to an educational setting (the aim is to improve their learning abilities)
  • an occupational therapist, who helps people improve the skills they need to carry out daily activities

Read more about education for people with learning difficulties and requesting a statement.

Behavioural problems

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

Read more about treating attention deficit hyperactivity disorder.

High blood pressure

Moderately high blood pressure can usually be brought under control 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 will require treatment with medication, such as angiotensin-converting enzyme (ACE) inhibitors.

Read more about treating high blood pressure.

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, your child will need regular eye examinations so that the status of the tumour can be closely monitored. If your child experiences symptoms, a number of medications can be used to help shrink the tumour.

Bone problems

Scoliosis

If your child develops an abnormally curved spine (scoliosis), the recommended treatment will depend on how severe the curvature is.

Mild cases may require no 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.

Read more about treating scoliosis.

Pseudarthrosis

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 that involve the bones of the limbs, surgery does not repair the bone. In this case, it is necessary to amputate a section of the limb in order to restore normal function. 

People with pseudarthrosis should be referred to specialist orthopaedic centres that are used to treating this complication.

Brain and nervous system problems

Tumours

Tumours that develop inside the brain or nervous system do not always cause symptoms, but they occasionally 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, the use of 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

Epilepsy can be treated with a number of different medications that help reduce the frequency of seizures. Read more about treating epilepsy.

Malignant peripheral nerve sheath tumour

If you are an adult with NF1 and you develop cancer in a section of your nerve tissue (known as malignant peripheral nerve sheath tumour or MPNST), surgically removing the tumour will usually be 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.

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Published Date
2013-08-27 17:21:24Z
Last Review Date
2013-04-15 00:00:00Z
Next Review Date
2015-04-15 00:00:00Z
Classification
Acoustic neuroma,Hypertension,Neurofibromatosis,Scoliosis

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