Neurofibromatosis type 1

Overview

Neurofibromatosis type 1 (NF1) is a genetic condition that causes tumours to grow along your nerves. The tumours are usually non-cancerous (benign) but may cause a range of symptoms.

Neurofibromatosis type 2 (NF2) is much less common than NF1. It's covered separately as it has different symptoms and causes.

Symptoms of neurofibromatosis type 1

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, the skin is affected, causing symptoms such as:

birthmarks known as cafe au lait spots, which are light or dark brown patches that can be anywhere on the body
soft, non-cancerous tumours on or under the skin (neurofibromas)
clusters of freckles in unusual places – such as the armpits, groin and under the breast
problems with the bones, eyes and nervous system

Certain health problems are often associated with NF1, such as learning difficulties. Less commonly, NF1 is associated with a type of cancer known as malignant peripheral nerve sheath tumours.

Causes of neurofibromatosis type 1

NF1 is caused by a faulty gene. If the NF1 gene is faulty, it leads to uncontrolled growth (tumours) developing in the nervous system.

In half of all cases of NF1, the faulty gene is passed from a parent to their child. Only one parent needs to have the faulty gene for their child to be at risk of developing the condition.

If either the mother or father has the faulty gene, there's a 1 in 2 chance that each child they have will develop NF1.

In other cases, the faulty gene appears to develop spontaneously (where there is no family history of NF1. It's unclear why this happens. If you have a child who develops NF1 spontaneously, it's highly unlikely any further children you have will also develop the condition.

However, if you do have a child who develops NF1 spontaneously, they can pass on the condition to any children that they have.

Diagnosing neurofibromatosis type 1

It's usually easy to diagnose NF1 in adults and older children by checking for the typical symptoms.

It may be diagnosed in babies who show symptoms of NF1 from birth. However, it's not always possible to make a firm diagnosis in early childhood because some symptoms take years to develop.

If NF1 is suspected, further tests such as scans, blood tests or a biopsy may be recommended. This is to assess whether your child has other symptoms or conditions associated with NF1.

If there's uncertainty about the diagnosis, your child may be able to have a blood test to see whether they have the faulty NF1 gene. However, the test is not completely reliable: around 5% of children who test negative for the faulty gene still develop NF1.

Before and during pregnancy

Couples with a family history of NF1 may wish to consider their options before having a baby. Your GP can refer you to a genetic counsellor to discuss your options.

These may include:

having a child with a donor egg or sperm
adopting a child
having a test during pregnancy – either chorionic villus sampling or amniocentesis to see if your baby will have NF1
pre-implantation genetic diagnosis – where eggs are fertilised in a laboratory and tested to make sure they don't have the NF1 gene, before being implanted into the womb

Treatment for neurofibromatosis type 1

There's currently no cure for NF1. Treatment involves regular monitoring and treating any problems as they occur.

Treatment can involve:

surgery – to remove tumours and improve bone abnormalities
medicine – to control secondary conditions, such as high blood pressure
physiotherapy
psychological support
pain management

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, that can reduce life expectancy.

NF1 and pregnancy

If you become pregnant while living with NF1, you should be able to have a healthy pregnancy.

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.

Support from charities

Nerve Tumours UK is a charity that aims to improve the lives of people with either type of neurofibromatosis.

For more information, you can visit the Nerve Tumours UK website, call its helpline on 07939 046 030 or email info@nervetumours.org.uk.

The Childhood Tumour Trust also provides information and support for young people and their families who may be affected by NF1.

NF1 and breast cancer

Women under 50 with NF1 have an increased risk of breast cancer and should start having breast screening appointments when they're 40 years old.

Information about you

If you or your child has NF1, your clinical team will pass information on to the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS).

This helps scientists look for better ways to prevent and treat this condition. You can opt out of the register at any time.

Find out more about the NCARDRS

Symptoms

The symptoms of neurofibromatosis type 1 (NF1) are often mild and cause no serious health problems. But some people will have severe symptoms.

The symptoms of NF1 can affect many different areas of the body, but it's unlikely someone will develop all of them.

The skin

Coffee-coloured patches

The most common symptom of NF1 is the appearance of painless, coffee-coloured patches on the skin, called café au lait spots. However, not everyone with café au lait spots has NF1.

The spots can be present at birth or develop by the time a child is 3 years old.

During childhood, most children with NF1 will have at least 6 café au lait spots around 5mm across. These grow to about 15mm during adulthood.

The number of 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.

Freckles

Another common symptom of NF1 is clusters of freckles in unusual places, such as the armpits, groin and under the breast.

Tumours on or under the skin

As a child gets older, usually during teenage years or early adulthood, they develop tumours 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 are purple.

The number of neurofibromas can vary. Some people only have a few, while others have them on large sections of their body.

Most neurofibromas are not particularly painful, but they may be visible, 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 problems with the bladder or bowels, such as urinary tract infections or constipation.

Learning and behaviour

Some children with NF1 develop learning and behavioural problems. It's unclear why this happens.

Children with NF1 who have a learning difficulty may have normal or slightly lower-than-average intelligence, but they can usually be taught at a mainstream school.

Attention deficit hyperactivity disorder (ADHD) affects around half of all children with NF1 and causes 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.

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 7 years of age are known to have the highest risk of developing this type of tumour. These tumours are often 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
one eye looking more prominent than the other

Younger children may be unable to explain that they have vision problems. You should be aware of any signs 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 a minimum of once a year until your child is at least 7 years old.

Another common feature of NF1 is the appearance of tiny, raised brown spots in the coloured central part of the eye (iris). These are known as Lisch nodules and do not usually cause any noticeable symptoms or vision problems.

High blood pressure

Some children with NF1 develop high blood pressure.

High blood pressure may be caused by narrowing of the artery to the kidney (renal artery stenosis). This requires specialist treatment if it's found to be causing your child's high blood pressure.

High blood pressure may also be caused by a phaeochromocytoma. This is a tumour of the adrenal glands that is usually benign. It's more common in adults than children.

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 should have regular blood pressure checks, usually at least once a year.

Physical development

Many children with NF1 have one or more problems affecting their physical development, including:

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 lower 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 causes curving (bowing) of the limb, usually in the tibia bone of the lower leg. The bone may fracture after a minor injury. The fracture does not heal completely, which affects the normal movement of the leg.

The brain and nervous system

Symptoms affecting the brain and nervous system are relatively common in NF1.

Many people with NF1 get migraines.

Some people develop brain tumours, although this is rare. 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

Some children with NF1 develop epilepsy, where a person has repeated seizures or fits. This tends to be a mild form of epilepsy that's usually controlled easily with medicine.

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. It's estimated that people with NF1 have around a 10% chance over their lifetime of developing a MPNST.

Most cases first develop when people are in their late 20s or early 30s, but they 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 did not have before, such as weakness, numbness or tingling in your arms and legs
loss of bladder or bowel control
difficulty breathing or swallowing

If you have any of these symptoms, contact the doctor in charge of your care as soon as possible.

Gastrointestinal tumour

Some people with NF1 can develop a gastrointestinal tumour (GIST), which may cause symptoms such as:

abdominal pain
changes in bowel habits – such as diarrhoea or constipation
bleeding from the bottom

Gastrointestinal tumours require management at a specialist centre.

Specialist centres

If you need specialist management, you should be referred to a specialist centre with experience in diagnosing and treating MPNST.

There are currently 2 centres, one in Guy's & St Thomas' NHS Foundation Trust in London and the other in the Central Manchester University Hospitals NHS Foundation Trust.

Treatment

Treatment for neurofibromatosis type 1 (NF1) involves regular monitoring and may include physiotherapy, psychological support and pain management. Any problems are treated by a team of health professionals.

If you develop complex problems, you'll usually be referred to one of two specialist NHS centres so a treatment plan can be drawn up. These are:

Monitoring

Most children with NF1 are advised to have a comprehensive examination each year. This may include:

a detailed skin examination to check for new plexiform neurofibromas – older children may also be monitored for neurofibromas
a vision test and an examination of both eyes
a bone assessment to check for problems such as curvature of the spine (scoliosis) or poorly healed bone fractures
behavioural assessments
blood pressure measurement
measuring their physical development
assessing their 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.

Adults with NF1 also need regular assessments. These may include:

detailed skin examination to check for neurofibromas
a bone assessment to check for problems such as curvature of the spine (scoliosis) or vitamin D deficiency
blood pressure measurement
neurological assessment
assessing emotional wellbeing and how their employment is going
assessing any learning problems – some adults may benefit from adult literacy classes

Skin problems

Café au lait spots

There's usually no need for treatment of café au lait spots, which are common in NF1. Sometimes they fade as people get older.

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 tumours on or under the skin (neurofibromas) may not require any treatment if they're small. However, treatment can be used if the neurofibromas are painful or causing emotional distress.

Plastic surgery is usually needed. The surgeon cuts the neurofibromas out of the body before resealing the skin.

Depending on the size and location of the neurofibromas, they may be able to be treated with laser surgery or an electric current (electrodessication) instead.

The results of surgery are usually good, although the procedure can leave some thickened scarring and there may occasionally 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 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.

You should consult a specialist neurofibromatosis centre for advice about removal of plexiform neurofibromas and other treatments that may be available.

Learning difficulties

If your child has a learning difficulty, support is available.

Contact the special educational needs co-ordinator (SENCO) in your child's school or nursery.

Contact your local council if your child isn't in a school or nursery.

As well as extra help in class, some children with NF1 require additional support from other professionals, such as:

a speech and language therapist
an educational psychologist, who helps improve learning abilities
an occupational therapist, who helps improve the skills needed to carry out daily activities

High blood pressure

Some people can control high blood pressure by making lifestyle changes including:

reducing the amount of salt in their diet
doing regular exercise
maintaining a healthy weight
moderating alcohol consumption and not smoking

Very high blood pressure requires treatment with medicine.

Optic pathway tumours

If your child develops a tumour inside the nerve connecting the eye and the brain (the optic nerve) that does not cause any symptoms, no immediate treatment is necessary. This type of tumour, called 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 to monitor the tumour. If your child experiences symptoms, chemotherapy can be used to help shrink the tumour.

Radiotherapy is not used for optic nerve tumours because it can cause problems with cancerous tumours, blood vessels, hormones and learning.

Bone problems

Scoliosis

Treatment for an abnormally curved spine (scoliosis) depends on how severe the curvature is.

Mild cases do not always require treatment because your child's spine may correct itself as they get older. Moderate cases can be treated using a back brace.

Surgery may be required to realign the bones of the spine into the correct position in severe cases of scoliosis.

Pseudarthrosis

Surgery can also be used to treat poorly healed bone fractures that disrupt the normal movement of the bones (pseudarthrosis).

Possible surgical options are to reconnect 2 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 does not 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

Tumours developing inside the brain or nervous system do not always cause symptoms, but they can disrupt the normal functions of the body.

If treatment is needed, it may involve surgery or drug treatment.

Radiotherapy for tumours

Radiotherapy should not be used to treat benign tumours as it can increase the risk of developing cancer.

It's sometimes used to treat malignant tumours on the advice of specialist doctors.

Epilepsy

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, called a malignant peripheral nerve sheath tumour (MPNST), surgical removal is usually recommended.

Radiotherapy and chemotherapy may be given after surgery to reduce the risk of the cancer coming back, although it's uncertain how effective these additional treatments are.

Glomus tumours

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 or ultrasound scan. They can be surgically removed.

The information on this page has been adapted by NHS Wales from original content supplied by

NHS website nhs.uk