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.