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.