Understanding neurofibromatosis
Neurofibromatosis is the most common rare genetic disease in Québec
Neurofibromatosis (NF) is a genetic disorder with two distinct forms: NF type 1 (NF1) and all types of schwannomatosis (SWN), which includes NF2-related schwannomatosis. NF causes tumours of various sizes to grow along nerves anywhere in the body. NF can also affect the development of other tissues such as skin and bone.
We invite you to watch our documentary, which sheds light on NF through touching testimonials from people affected by the disease. Sarah Lapointe (CHUM) and Sébastien Perreault (CHU Ste-Justine), both neurologists and neuro-oncologists, also explain NF very well.
Causes of NF
Around half of all neurofibromatosis sufferers have a genetic predisposition to the disease. A single NF carrier gene from a single parent is sufficient for the disease to develop, and each child of an affected parent has a 50% risk of developing the disease. This is why NF is considered a hereditary disease. The majority of genes involved in neurofibromatosis have been identified.
In the remaining 50% of the affected population, neurofibromatosis is the result of a spontaneous, non-hereditary genetic mutation. These people have no family history of the disease.
There are different types of mutation (inherited or spontaneous), as the severity of the disease depends on the type of mutation.
Here’s a picture that explains how genes are passed on.
FAQ
Neurofibromatosis (NF) is a genetic disorder. It is a skin, nervous system and bone disorder that is 50% hereditary, meaning that the defective NF gene has been passed on to the child by one or other of the parents. In the other half of cases, it is the result of a spontaneous genetic mutation.
It should be noted that NF is a rare disease that affects both men and women and makes no ethnic distinction, making it one of the most common genetic or hereditary disorders. Its symptoms manifest themselves differently from one person to the next. There are now two distinct forms of NF: neurofibromatosis type 1 (NF1) and schwannomatosis (SWN), which includes NF2-related schwannomatosis (NF2-SWN), formerly known as neurofibromatosis type 2.
NF1 is the most common form, with one in every 2,500 babies born with the disease every year. It can cause a variety of manifestations, including tumour growth along the nerves, cancer, bone abnormalities and learning disabilities. The number of people affected is estimated at over 4,000 in Quebec and over 20,000 in Canada. However, there is as yet no precise system for determining the exact number of people affected.
Schwannomatosis (SWN) is the least common and most recently identified form of NF. Approximately one in 20,000 people will eventually be diagnosed with schwannomatosis, and one in 70,000 if NF2-related schwannomatosis (NF2-SWN) is excluded. Schwannomatosis is a generic term for several genetic conditions that cause benign tumours to develop on the nerves. NF2-related schwannomatosis is the most common type of SWN, affecting 1 in 25,000 people. It is characterized by benign tumours called vestibular schwannomas on the eighth cranial nerve, which is the nerve that carries sound and balance information to the brain.
It’s important to remember that NF is not contagious, and should not be confused with other rare diseases, such as elephant man disease, which is called Proteus syndrome.
For NF1, the signs are:
Brown spots, six or more, 0.5 cm in diameter in children and 1.5 cm in diameter in adults: they appear at birth or before the age of two
Small freckles in the axilla (armpit) or groin area
Neurofibromas, which are small masses of cells under or on the skin, near a vital organ or diffusely infiltrating tissues; the result of cell overgrowth, these benign tumours, two or more in number, usually develop at puberty or during pregnancy
Skeletal anomalies
Lisch nodules: these are small freckles in the iris of the eye that are of no consequence.
Epileptic seizures.
For schwannomatosis, the signs are:
Hearing loss
Eye problems
Unmanageable pain anywhere in the body
For NF2-related schwannomatosis, the signs are:
Hearing loss
Ringing in the ears
Balance problems
Facial weakness
Convulsions
Visual impairment
Other problems due to tumours of the central nervous system
The complications listed below are present in about 25% of sufferers, which is why it is so important for all sufferers to have regular check-ups with a doctor who is familiar with the problems associated with neurofibromatosis.
Possible complications include
Disfigurement, caused by an internal tumour
Scoliosis, i.e. an S-shaped deviation of the spine
Congenital bone abnormalities that can lead to bone fragility, such as osteopenia or osteoporosis.
Macrocephaly: many children with NF have a larger-than-average head circumference. This condition causes no problems for the child.
Learning disabilities. Between 40% and 60% of people with NF will experience learning difficulties, many of them non-verbal. Hence the importance of early detection of the disease and the introduction of appropriate educational measures and teaching techniques, including for adults. Cooperation between the medical, school and family environments is a prerequisite for affected children to develop to their full potential.
NF is a disease whose evolution is difficult to determine, and whose manifestations and consequences vary. But as long as sufferers benefit from strong family and social support and adequate health care throughout their lives, they generally lead normal, productive lives.
It’s very important to take steps to obtain medical follow-up. Your family doctor will be able to monitor your symptoms and refer you to a specialist in NF, such as a neurologist, geneticist, ophthalmologist and so on. Don’t hesitate to ask questions.
You can also visit the “Consult a specialist” section of our website to find an NF clinic in your area.
Other neurofibromatosis sufferers can also help and support you through the disease. You can visit our Facebook page and contact us at the Quebec Neurofibromatosis Association.
Treatments are available for the complications of the disease and the tumours it can cause. For example, neurofibromas that cause discomfort and 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. Surgery may also be beneficial for severe scoliosis, but a prosthesis may suffice for less pronounced scoliosis.
In some cases, vitamin D can be given, high blood pressure treated, anti-epileptic drugs administered, etc.
In addition, certain drugs (chemotherapy) or radiotherapy may be used.
Koselugo (sélumétinib) is the first and only pediatric therapy approved by HEALTH CANADA for the treatment of NF1 with plexiform neurofibroma (PN), and is currently available in Quebec. For patients with NF1 with PN, this good news fills an important need, as there were no options for patients with inoperable NF1 with PN. In a Canadian experiment, 82% of patients confirmed a durable response, i.e. a halt in disease progression, 66% of patients experienced shrinkage (20% tumour reduction), clinically significant improvement in pain intensity and better functionality.
To find out more about Koselugo, please visit: https://koselugo.com/
At present, for NF2-related schwannomatosis, there is no official cure, but promising advances in research are underway. However, pain management is generally an integral part of care. People with schwannomatosis are best served in an NF clinic, where multidisciplinary specialists experienced in schwannomatosis can administer pain management protocols that have proven effective for people with the disease.
Research is ongoing and enormous progress has been made over the past fifteen years. The NF1 and NF2 genes responsible for this condition and their respective chromosomes have been identified. To understand the origin and evolution of the genetic disturbance, research is carried out in the laboratory. It’s an immense task, but also a sign of hope, as researchers believe they can find effective treatments.