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.