Neurofibromatosis type 1

About NF1

Neurofibromatosis type 1 (NF1) is one of the most common genetic diseases, affecting around 1 in 2,500 people. It is a genetic disorder linked to an abnormality (a mutation) in the NF1 gene. It is a skin, nervous system and bone disorder that is either inherited from a
parent, or newly arrived in a person without the parents having it. About half of NF1 cases are inherited from a parent, meaning that the genetic mutation causing NF was passed on to the child by one or other of the parents. In the other half of cases, NF1 is the result of a
spontaneous genetic mutation, meaning that it was not transmitted by a parent. What’s important to know is that people with NF1, whether they inherited it from a parent or contracted it through spontaneous mutation, have a 50% chance of passing it on to each of their children.

Symptoms

Symptoms vary widely from patient to patient, even within the same family. This is what makes the disease so complex. NF1 mainly affects the skin and nervous system. There are mild forms that pass almost unnoticed, but there are also more severe forms. Unfortunately, we cannot predict the level of disease severity in a person who develops NF1. For example, a parent with few symptoms could transmit the disease to his or her child at a higher level of severity.

The first signs of NF1 are often visible at birth or during childhood, but sometimes symptoms go unnoticed until adulthood. The main signs of NF are seen in the skin (cutaneous symptoms), eyes, nerves, bones and blood vessels.

To clarify matters, here are the symptoms to look for in each of the systems listed above.

Cutaneous symptoms (skin)

  • Light brown oval spot
  • Small, light-brown spots, less than 5 mm in size, like freckles, in folds of the skin, for example, under the armpits, in the groin, under the breasts and on the neck. These are known as lentigines.
  • Non-cancerous (benign) tumours, called cutaneous neurofibromas, form small bumps on the skin. These neurofibromas do not undergo malignant (cancerous) changes. They may occasionally cause mild discomfort due to pruritus (itching), but usually do not require specific treatment. They can be removed as needed if they cling to clothing or for aesthetic reasons. When removal is considered, children should be referred to a plastic surgeon to discuss risks such as reappearance or hypertrophic scarring (visible scars).
  • Non-cancerous tumours called plexiform neurofibromas affect several nerves. They can grow large and invade other tissues and bones. Some are internal and can be seen little or not at all, while others are in the form of gelatinous masses where the skin is sometimes darker. Regular follow-up is important, as in 1-10% of cases, plexiform neurofibromas can become cancerous. Among NF1 patients, almost 1 in 3 has a plexiform neurofibroma.

Eye symptoms

  • Red-brown spots in the iris (the coloured part of the eye) are known as Lisch nodules; fortunately, they do not affect vision and cause no other symptoms
  • Glioma (tumour) on the optic nerve, which connects the eye to the brain; almost half of these tumours cause no symptoms
  • Glaucoma, an increase in pressure in the eye, which damages the optic nerve and can lead to loss of sight

Neurological symptoms

  • Learning difficulties: 40-60% of people with NF1 have learning difficulties, many of which are non-verbal
  • Macrocephaly, meaning above-average head size
  • Epileptic seizures
  • Brain tumours (benign and malignant) can cause weakness, reduced skin sensitivity, balance problems, difficulty swallowing, and more, depending on where they are located

Bone symptoms

  • Bone malformation (dysplasia)
  • Abnormal curvature of the spine (scoliosis)
  • Brittle bones (osteopenia or osteoporosis, low vitamin D levels)

Blood vessel symptoms

  • High blood pressure (hypertension)
  • Deformation of blood vessels that can cause stroke, cardiovascular disease, narrowing of arteries leading to the kidneys, or other disorders elsewhere in the body

If you ever experience one or more NF1-like symptoms, it’s very important to tell your family doctor, who will be able to refer you to an NF specialist.

If you need to consult a team of NF specialists, they will determine whether you have the disease based on several criteria: your various symptoms, whether or not the disease runs in your family, and so on. If requested, you can even undergo a genetic test to determine whether there is a mutation in the NF1 gene.

Treatments

At present, there are treatments that can act on the complications of the disease and the tumours it can engender. For example, neurofibromas that cause discomfort or pain, interfere with functioning or are cancerous can be removed by surgery. The important thing to remember is that not all neurofibromas need to be removed.

Rarely, when tumours are cancerous, other treatments may be used, such as chemotherapy or radiotherapy. Treatments are also being tested for inoperable tumours.

For children aged 2 and over who have NF1 with symptomatic plexiform neurofibromas (PN) that cannot be completely removed by surgery, there is now a first treatment approved by Health Canada, Koselugo (selumetinib).

In some cases, we can give vitamin D, treat high blood pressure, give anti-epileptic drugs, and so on.

A word of advice: keep a close eye on your little lumps under the skin (subcutaneous or plexiform neurofibromas). Look to see if they’re growing fast, starting to hurt constantly, causing loss of function (weakness or reduced sensation, for example). If so, consult your doctor without hesitation.

It’s important to remember that even if you have NF1, it’s possible to live your life to the fullest. But it’s very important to have regular follow-ups with your family doctor and your team of NF1 specialists. The sooner you are taken care of, the less likely you are to face serious complications.