Neurofibromatosis or “Von Recklinghausen’s disease” are more or less rare genetic diseases. Type 1 is associated with an increased risk of cancer and a decrease in life expectancy of about 10-15 years compared to the general population.
Definition: what is neurofibromatosis?
There is not “one” but “many” neurofibromatosis. Neurofibromatosis are genetic diseases who are among the most frequent rare diseases. “This group is quite heterogeneous, explains it to us Professor Pierre WolkensteinDean of the Faculty of Medicine of Paris Est Créteil, Head of the Dermatology Department, dermatologist, oncologist, coordinator of the reference center for neurofibromatosis. Wolkenstein. Their common point is give benign tumors in the majority of cases. The trademark is the nerve sheath tumor.”
What is neurofibromatosis type 1?
Neurofibromatosis type 1 (or Recklinghausen’s disease) is most common neurofibromatosis (1 birth in 3000). It is a genetic disease that alters the NF1 gene, a tumor suppressor gene that, when inoperative, does not suppress possible tumors. It is defined by the development of tumors –neurofibromas- on the body and inside the body associated with café-au-lait spots, freckles called “lentigines” in the folds of the skin and other symptoms such as a context of bone malformation (abnormalities of the long bones, scoliosis, pseudarthroses, etc.). And, says Prof. Wolkenstein “in 40% of cases there are learning difficulties : people have a normal intelligence quotient but have significant academic difficulties. And, lastly, sometimes there are tumors located on the optic nerve, this is called “optic pathway glioma”.
What is neurofibromatosis type 2?
Neurofibromatosis type 2 is much rarer : it concerns 1 birth in 25,000 (HAS). “This disease causes central nervous system tumors, explains Prof. Wolkenstein. It is schwannomas (or neuromas), essentially pairs of cranial nerves and in particular the vestibular nerve. Associated with other tumors called meningiomas.” It results from a deficiency in the NF2 gene. age means of onset of clinical signs is located between 18 and 24 years old. A start at any age is however possible
What is neurofibromatosis type 3?
Neurofibromatosis type 3 rather called today “schwannomatosis” is a disease that causes schwannomas but does not cause cranial nerve tumors.
When one of the two parents is affected, the risk of transmission to the offspring is 50%.
What are the causes of neurofibromatosis?
All these neurofibromatosis are linked to a similar mechanism: the presence of an abnormality in genes which are usually tumor suppressor genes. “Most neurofibromatosis is transmitted autosomally dominantly. explains Prof. Wolkenstein. when one of the two parents is affected, the risk of transmission to offspring is around 50%. On the other hand, the new mutation rate is high, which means that 50% of cases, on average, come from parents who do not have the disease.“These genetic diseases are extremely variable from one individual to another within the same family.
What are the symptoms of neurofibromatosis?
Neurofibromatosis type 1 is characterized by:
- pigment spots of light brown color, rounded or oval, variable in size.
- Of the lentigines resembling freckles of different location, under the arms, in the crease of the groin and at the level of the neck.
- Of the cutaneous neurofibromas which are benign (non-cancerous) tumours.
- Of the optic pathway gliomas.
- Of the bone abnormalities.
- Of the brain tumors
- Dysplasia,
- Scoliosis
- Pubertal disorder and failure to thrive
- Neurofibromas can develop on one or more nerve roots from the spinal cord) as well as cognitive disorders with learning difficulties.
Neurofibromatosis type 2 manifests itself by tumors of the central nervous system intracranial and pericranial schwannomas or neuromas and meningiomas. There clinical presentation of the child differs from that of the adult and is more frequently characterized by:
- skin involvement (subcutaneous tumours, intradermal papillary tumours),
- eye damage (juvenile cataract, paralysis of the ocular motor nerve),
- mononeuropathy (peripheral facial palsy, one hand deficit)
- or finding an isolated meningioma or schwannoma.
What is the life expectancy in case of neurofibromatosis?
► Type 1: “It’s a disease which globally reduces the life expectancy of patients only slightly (from 10 to 15 years compared to the general population according to the HAS). On the other hand, there are complications that can be fatal, in particular the transformation into cancer of neurofibromas, so-called malignant nerve sheath tumors which are extremely serious complications.“.
► Type 2: “This disease is more severe in terms of prognosis than neurofibromatosis type 1 and life expectancy is significantly reduced“.
When a geneticist, a dermatologist, a surgeon, an ENT, a neurologist or an oncologist encounters a suspicion of neurofibromatosis, he refers his patient to the expert reference center so that the diagnosis can be confirmed or ruled out. On the basis of clinical examinations, this diagnosis is then refined by a blood sample to extract the DNA and sequence it in order to target the genes that are involved (NF1, NF2…) and the abnormality that will be found will be the molecular cause of neurofibromatosis.
| Situation A. In the absence of a parent with NF1, an individual is diagnosed with NF1 when at least two of the following criteria are present: |
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*If only TCL and lentigines are present, the most likely diagnosis is that of NF1, but the patient may exceptionally present with another pathology, including Legius syndrome. # At least one of the two types of pigmented lesions (TCL or lentigines) must be of bilateral topography
**Dysplasia of a sphenoid wing is not an independent criterion in the case of ipsilateral orbital plexiform neurofibroma.
| Situation B. In a child who has a parent meeting the diagnostic criteria for NF1 specified in A, the presence of at least one criterion of A allows the diagnosis of NF1 to be made. |
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What is the treatment for neurofibromatosis?
Today the treatment of all tumors is surgical. “We are developing more and more targeted therapies derived from cancer research, explains Prof. Wolkenstein. In neurofibromatosis type 2, there is a drug calledAvastin® which is quite effective on the volume of schwannomas and in neurofibromatosis type 1, these are drugs that are called MEK inhibitors which are a great hope for decreasing the volume of tumors“. he specifies.
Associations for neurofibromatosis
Various associations exist to support and guide patients and their relatives:
Thanks to Pr. Pierre Wolkenstein, Dean of the Faculty of Medicine of Paris Est Créteil, Head of the Dermatology Department, dermatologist, oncologist, coordinator of the neurofibromatosis reference center.
Sources:
Neurofibromatosis, Transparency Committee, Opinion January 5, 2022, HAS
National Diagnostic and Treatment Protocol (PNDS) Neurofibromatosis 2, HAS, September 2021