Neurofibromatosis (NF) is one of the most common genetic conditions and can affect anyone, regardless of family history, race, gender, or ethnic background.
NF1 affects approximately one out of every 3,000 individuals. NF2 affects one out of every 25,000 individuals. A third classification, Schwannomatosis, is a rare form of NF that has only recently been recognized and appears to affect around 1:40,000 individuals. It is less well understood than NF1 and NF2, and features may vary greatly between patients.
Both NF1 and NF2 are characterized by the growth of benign tumors called neurofibromas. These tumors can grow anywhere in the body where there are nerve cells. This includes nerves just under the surface of the skin, as well as nerves deeper within the body, spinal cord, and/or brain.
In NF1, neurofibromas most commonly grow on the skin or on the nerve to the eye. A tumor which grows on the nerve to the eye is called an optic glioma and, if it grows large enough, can cause problems with vision, including blindness. To learn more about the features or diagnosis visit our NF1 page.
In NF2, neurofibromas most commonly grow within the spinal cord or brain. Specifically, the tumors are found on the nerves to the ear, called acoustic neuromas, or the nerves for balance, called vestibular schwannomas. Acoustic neuromas, if large enough, can lead to deafness. To learn more about the features or diagnosis visit our NF2 page.
How does a person get NF?
NF is caused by a change in our genetic material. NF1 is caused by a change in a gene carried on chromosome 17. NF2 is caused by a change in a gene carried on chromosome 22.
The change in the genetic material that causes NF1 and NF2 can be inherited from a parent, referred to as autosomal dominant inheritance, or it can occur spontaneously at conception. The NF gene is always present at birth, though symptoms may not appear until later in life.
Autosomal Dominant Inheritance
If either parent has NF, there is a 50% chance with each pregnancy that the gene causing NF will be passed on to the child. There is no way to predict whether a child who inherits the gene will be affected more severely, the same, or less than the parent. If one parent has an autosomal dominant condition such as NF, there is a 50% chance that it will be passed to each child.
In approximately 50% of cases, NF occurs in an individual who has no family history of the disorder. Anyone can be born with NF. This happens when there is a spontaneous change in the genetic material carried by either the sperm or the egg when pregnancy begins. There is nothing a parent can do or not do to cause this change. Once a person has the changed gene that causes NF, he or she will have NF and therefore have a 50% chance of passing the gene on to his or her children.
Neurofibromatosis type 1 and type 2 both occur in mosaic forms. Mosaicism results from somatic mutations. Early somatic mutations cause generalized disease, clinically indistinguishable from nonmosaic forms. Later somatic mutation gives rise to localized disease often described as segmental. In individuals with mosaic or localized manifestations of neurofibromatosis type 1 (segmental neurofibromatosis type 1), disease features are limited to the affected area, which varies from a narrow strip to one quadrant and occasionally to one half of the body. Distribution is usually unilateral but can be bilateral, either in a symmetric or asymmetrical arrangement. Patients with localized neurofibromatosis type 2 have disease-related tumors localized to one part of the nervous system; for example a unilateral vestibular schwannoma with ipsilateral meningiomas or multiple schwannomas in one part of the peripheral nervous system. The recognition of mosaic phenotypes is important. Individuals with the mosaic form, even with a generalized phenotype, are less likely to have severe disease. They also have lower offspring recurrence risk than individuals with the nonmosaic form. The mosaic forms of neurofibromatosis provide a good example of the effects of somatic mutation. It is increasingly recognized that mild and unusual forms of many dominantly inherited disorders are caused by the same mechanism.