What is Neurofibromatosis?It is known as neurofibromatosis to a set of rare diseases of genetic cause and are mainly characterized by the development of multiple benign, i.e. non-cancerous, tumors in different nerves of the body and the skin; as well as the formation of spots in the variations in pigmentation (areas hyperpigmented or hypopigmented) skin.
This disease was first described by a German physician named Friedrich Daniel von Recklinghausen in 1882, and from that moment was coined the term of Von Recklinghausen's disease or neurofibromatosis type 1 (NF1) as it is known at present.
There is also the neurofibromatosis type 2 (NF2) or acoustic neurofibromatosis, but it hardly constitutes 5% of all cases of neurofibromatosis.
The prevalence of neurofibromatosis type 1 is approximately one case among 3,000 people, so it is estimated that there must be about two million affected in the world. Regarding neurofibromatosis type 2, it is estimated that its prevalence is a case between 45,000 people.
Causes of neurofibromatosisScientific evidence has shown that in the case of the neurofibromatosis type 1 (NF1) there is an alteration in a gene (mutation) on chromosome 17. This gene regulates the production of a protein called neurofibromin, whose main function is to inhibit the appearance of tumors. Mutations occur spontaneously in 50% of patients from unknown causes, and the other 50% of the cases the mutation is inherited from parents to children in a way autosomal dominant.
But what the dominant autosomal inheritance? It is the heritage not sex-linked, which occurs when the father or the mother to her son inherit a gene with a mutation that is capable of causing disease, because the mutated gene dominates the normal gene. Then if one of the parents is a carrier of disease and the other is not, the probability that each son inherit the mutated gene is 50%.
In the neurofibromatosis type 2 (NF2) mutation is located in a gene of chromosome 22. Around 33 mutations in this gene have been described, and all cause the loss of the ability to suppress the formation of tumors. It is inherited from parents to children, in the same way as NF1 autosomal dominant, and you can also find cases of absence of family history because we have generated spontaneous mutations in the affected patient.
Symptoms of neurofibromatosis type 1 (NF1)There are three main signs that define the majority of patients with neurofibromatosis type 1 (NF1) and are called major signs:
- Light brown skin spots, known as Café au lait spots, which circumscribe areas rounded or oval, are flat and are caused by an excess in the accumulation of melanin (skin pigment). They tend to appear since childhood (from the first year of life) and its size increases as the child grows. In terms of their number, they can vary from one or two spots to be more than six spots; they are considered very valuable from the diagnostic point of view, because they occur in 10-20% of patients with NF1. They are found mainly in the skin of the trunk, also observed small freckles in other areas such as the neck, armpits, or groin region. These stains do not have treatment, but have no risk of malignant transformation, i.e., do not cause skin cancer.
- Neurofibromas, which can be dermal (are benign tumors that occur in skin and nerves); they are of variable size, shape and coloration. They appear during puberty and adolescence progressively increasing throughout life. Do not produce pain, but if itching or stinging. There is a type of neurofibroma affecting large groups of nerves known as plexiform neurofibromas, which it may have babies affected by the disease at the time of the birth. Another type of neurofibromas can affect vision, and are those who are located in the optic nerve (second cranial nerve) and the retina, thus hindering the passage of nerve impulse to the brain from the outside world.
- The so-called Lisch nodules (hamartomas pigmentary): are rounded elevated lesions of yellow color which affect the iris (pigmented area of the eye). 1 over six years are observed in 90% of patients with neurofibromatosis type. These nodules do not alter the patient's visual ability and are difficult to observe with the naked eye, so it must be evaluated by specialists in Ophthalmology (through a slit-lamp).
Some complications that can occur in patients with NF1 are: difficulty to develop the language, learning disabilities which can occur in up to 50% children, deviation of the spine (scoliosis), malignant tumors of muscles and nerve endings (neurosarcomas), elevation of blood pressure, pathological curvatures of the bones of the leg (tibia and fibula) and that predispose to fractures, seizures (epilepsy), among others.
Symptoms of neurofibromatosis type 2 (NF2)The neurofibromatosis type 2 (NF2) presented as most relevant characteristic the emergence of benign tumors on the nerve, which is responsible for hearing, i.e. the par 8th cranial or nerve vestibulocochlear, which also has participation in the maintenance of posture and balance.
Tumors often affect the two ears, being able to appreciate the onset of symptoms at the beginning of adolescence. Then the patient complains of two main symptoms: progressive hearing or deafness, and frequent falls loss, problems with balance.
In the skin, Milky coffee spots also exist in this type of neurofibromatosis, but less frequently than in NF1. The spots are round edge flat and darken in the influence of the Sun on them. They have no risk of malignization and also do not have treatment.
From the eye point of view, patients with NF2 may present opacities in the lens (cataracts).
Among the complications of neurofibromatosis type 2 can be found: benign tumors of the brain, this causes an increase in pressure inside the skull (increased intracranial pressure), causing severe headaches, vomiting, blurred vision and even seizures. It can also be complicated with benign tumors in the spinal column and other benign tumors on the skin called schwamnomas, which are painful, in contrast to dermal neurofibromas in NF1, which are painless.
Diagnosis of neurofibromatosisThe signs and symptoms of the patient are key to the diagnosis of neurofibromatosis. Thus, multiple benign tumors of skin, nerves and the Café au lait spots, as well as the knowledge of family history are of vital importance.
Imaging studies featured in these pathologies are computed axial tomography (CT) and the magnetic resonance (NMR), which allow the detection of brain tumors, spine and tumors of the auditory nerve. Tests that assess the proper functioning of the conduction of sound through hatred should be performed to assess the sense of hearing.
In some cases, it may be necessary to do a biopsy of the neurofibromas to help confirm the diagnosis.
From the genetic point of view, the tests are performed by extracting DNA from the patient and their relatives in order to detect possible mutations responsible for the disease, chromosome 17 for neurofibromatosis type 1, both chromosome 22 to neurofibromatosis type 2.
Genetic counseling: when any of these conditions are detected in a family and one of their members manifest desires of paternity or maternity, there are two possibilities:
- Preimplantation genetic diagnosis, which allows you to select a healthy embryo for its later implantation into the womb.
- Prenatal diagnosis, which would be conducted by the detection of any of the mutations in the fetal cells during pregnancy, either by villus sampling biopsy, amniocentesis or ultimately funiculocentesis.
Treatment of neurofibromatosis· As a high percentage of rare and genetic diseases, there is currently no specific treatment for neurofibromatosis. It is recommended that patients should be managed by a multidisciplinary group of specialists such as pediatricians, neurosurgeons, ophthalmologists, dermatologists, geneticists, oncologists and psychologists, among others.
· Neurofibromas, depending on their location in the body, if they commit a vital organ, if they cause pain or not, they should be evaluated for their possible surgical removal. If the malignant transformation of some of the tumors detected other targeted therapies to treat this tumor in particular will be needed.
· The management of chronic pain with painkillers, antidepressants and drugs for anxiety (anxiolytic) is necessary in some patients with neurofibromatosis.
Prognosis of neurofibromatosis· If there are no complications, the life expectancy of people suffering from neurofibromatosis can become very similar to the one of a healthy individual, however, if they develop a malignant tumor (cancer) their expectations of life could be shortened.
· The most important thing is that diagnosis is made as soon as possible and awareness of the disease. Both the patient and family members should receive the necessary education for the management of the disease and know their potential complications. Some patients who have learning and language problems can suffer school failure and social problems, so it is good to detect it to try to give solution.