Neurofibromatoses are genetic diseases that predispose to the development of tumors of the nervous system. There are two main forms: neurofibromatosis type 1 and neurofibromatosis type 2. This disease cannot be treated. Only the complications are treated.

Definition

Neurofibromatosis is one of the most common genetic diseases. Autosomal dominantly inherited, they predispose to the development of nervous system tumors. 

There are two main forms: neurofibromatosis type 1 (NF1) which is also called Von Recklinghausen’s disease and type 2 neurofibromatosis called neurofibromatosis with bilateral acoustic neuroma. The severity of these two diseases varies widely. These are progressive diseases. 

Causes 

Type 1 neurofibromatosis is a genetic disease. The responsible gene, NF1, located on chromosome 17, alters the production of neurofibromin. In the absence of this protein, tumors, most often benign, develop. 

In 50% of cases, the gene comes from a parent affected by the disease. In the other half of cases, type 1 neurofibromatosis is due to a spontaneous genetic mutation. 

Type 2 neurofibromatosis is a genetic disease. It is due to the alteration of a tumor suppressor gene carried by chromosome 22.

Diagnostic 

The diagnosis of neurofibromatosis is clinical.

The diagnosis of type 1 neurofibromatosis is made when 2 of the following signs are present: at least six café-au-lait spots of more than 5 mm in their largest diameter in pre-pubertal individuals, and of more than 15 mm in pubescent individuals, at least two neurofibromas (benign non-cancerous tumors) of any type or plexiform neurofibroma, axillary or inguinal lentigines (freckles), optic glioma, two Lisch’s nodules, characteristic bone lesion such as sphenoid dysplasia , thinning of the cortex of long bones with or without pseudarthrosis, a first-degree relative with NF1 according to the above criteria.

The diagnosis of type 2 neurofibromatosis is made in the presence of several criteria: presence of bilateral vestibular schwannomas (tumors in the nerve connecting the ear to the brain) visualized on MRI, one of the parents suffering from NF2 and a unilateral vestibular tumor or two of the following: neurofibroma; meningioma; glioma;

schwannoma (Schwann cell tumors surrounding the nerve; juvenile cataract.

The people concerned 

Nearly 25 people in France have neurofibromatosis. Type 000 neurofibromatosis represents 1% of neurofibromatosis and corresponds to the most frequent of the autosomal dominant diseases with an incidence of 95/1 to 3 births. Less common type 000 neurofibromatosis affects 3 in 500 people. 

Risk factors 

One in two patients has a risk of transmitting type 1 or type 2 neurofibromatosis to their children. The siblings of a sick person have a one in two risk of being also affected if one of the two parents has the disease.

Type 1 and type 2 neurofibtomatosis do not cause the same symptoms. 

Symptoms of type 1 neurofibromatosis

Skin signs 

Skin signs are the most frequent: presence of café au lait spots, light brown in color, rounded or oval; lentigines (freckles) under the arms, in the crease of the groin and on the neck, more diffuse pigmentation (darker skin); cutaneous tumors (cutaneous neurofibromas and subcutaneous neurofibromas, plexiform -mixed cutaneous and subcutaneous neurofibromas).

Neurological manifestations

They are not found in all patients. It may be glioma of the optic pathways, brain tumors which may be asymptomatic or give signs such as, for example, a reduction in visual acuity or a protrusion of the eyeball.

Eye signs 

They are linked to the involvement of the eye, eyelids or orbit. These may be Lisch’s nodules, small pigmented tumors of the iris, or plexiform neurofibromas in the eye socket. 

Having a large skull (macrocephaly) is quite common. 

Other signs of type 1 neurofibromatosis:

• Learning difficulties and cognitive impairment 
• Bone manifestations, rare
• Visceral manifestations
• Endocrine manifestations 
• Vascular manifestations 

Symptoms of type 2 neurofibromatosis 

The telltale symptoms are often hearing loss, tinnitus and dizziness, due to the existence of acoustic neuromas. The main feature of NF2 is the presence of bilateral vestibular Schwannomas. 

Eye damage is common. The most common eye abnormality is an early onset cataract (juvenile cataract). 

Skin manifestations are frequent: plaque tumor, schwannomas of the peripheral nerves.

There are currently no specific treatments for neurofibromatosis. Treatment consists of managing the complications. Regular monitoring in childhood and adulthood can detect these complications.

Example of management of complications of type 1 neurofibromatosis: cutaneous neurofibromas can be removed surgically or by laser, chemotherapy treatment is set up to treat progressive gliomas of the optic pathways.

Type 2 neurofibromatosis tumors are treated with surgery and radiation therapy. The major therapeutic stake is the treatment of bilateral vestibular schwannomas, and the management of the risk of deafness. The brainstem implant is a solution for the rehabilitation of the hearing of patients who have been deafened by the disease.

Neurofibromatosis cannot be prevented. There is also no way to prevent the manifestations of the disease in people in people carrying the gene for neurofibromatosis type 1 and type 2. Regular monitoring can detect complications to manage them. 

The pre-implantation diagnosis makes it possible to re-implant embryos without the genetic defect.