A neurofibromatosis is a group of rare genetic diseases characterized by the development of multiple benign tumors in the nerves of the body and the skin and the formation of spots.
Neurofibromatosis is a set of rare diseases of a genetic cause that is mainly characterized by the development of multiple benign tumors. That is non-cancerous ones, in the different nerves of the body and the skin, and the formation of spots on the skin with variations in its pigmentation (hyperpigmented or hypopigmented areas).
This disease was first described by a German doctor named Friedrich Daniel von Recklinghausen in 1882. From that moment on, the term von Recklinghausen’s disease or neurofibromatosis type 1 (NF1) as it is known today was coined.
There is also neurofibromatosis type 2 (NF2) or acoustic neurofibromatosis, but it constitutes only 5% of all neurofibromatosis cases.
The prevalence of type 1 neurofibromatosis is approximately one case in 3,000 people, so it is estimated that about two million are affected in the world. Regarding type 2 neurofibromatosis, it is estimated that its prevalence is one case in 45,000 people.
Causes of neurofibromatosis
Scientific evidence has shown that in the case of 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 primary function is to inhibit tumor appearance. Mutations can appear spontaneously in 50% of patients for unknown causes, and in the other 50% of cases, the mutation is inherited from parents to children in an autosomal dominant manner.
But what does autosomal dominant inheritance mean? It is inheritance not linked to sex, which occurs when the father or mother inherits a gene with a mutation capable of causing disease because the mutated gene dominates the normal gene. So if one parent is a carrier of the disease and the other is not, the probability that each child inherits the mutated gene is 50%.
In neurofibromatosis type 2 (NF2), the mutation is located in a gene on chromosome 22. About 33 mutations in this gene have been described, and all-cause loss of the ability to suppress tumor formation. It is inherited from parents to children in the same way as autosomal dominant NF1, and cases of absence of family history can also be found because spontaneous mutations have been generated in the affected patient.
Symptoms of neurofibromatosis type 1 (NF1)
Three main signs define most patients with neurofibromatosis type 1 (NF1), and they are the so-called major signs:
- Light brown spots on the skin, known as café au lait spots, circumscribing rounded or oval areas, are flat and are caused by an excess accumulation of melanin (skin pigment). They usually appear from childhood (from the first year of life), and their size increases as the child grow. Their number can vary from one or two spots to more than six spots; they are considered very valuable from a diagnostic point of view, as they occur in 10% -20% of patients with NF1. They are mainly found on the skin of the trunk. Small freckles are also observed in other areas such as the neck, armpits, or groin region. These spots have no treatment, but they do not have a risk of malignancy. That is, they do not cause skin cancer.
- The neurofibromas, which may be dermal (benign tumors presented in skin and nerves), are variable, shape and coloration. They appear during puberty and adolescence, increasing progressively throughout life. They do not cause pain, but they do itch or sting. A type of neurofibroma affects large groups of nerves known as plexiform neurofibromas, which can occur in babies affected by the disease at birth. Another type of neurofibromas can affect vision and is located in the optic nerve (second cranial nerve) and the retina, making it difficult for the nerve impulse to pass from the outside world to the brain.
- The so-called Lisch nodules (pigmentary hamartomas): are raised, rounded yellow-brownish lesions that affect the iris (pigmented area of the eye). They are seen in 90% of patients with type 1 neurofibromatosis older than six years. These nodules do not alter the visual capacity of the patient. They are difficult to observe with the naked eye, so they must be evaluated by specialists in ophthalmology (through a slit lamp).