What is neurofibromatosis?

Neurofibromatosis (NF, or "the neurofibromatoses") is a group of diseases with some common symptoms. For a long time doctors did not realize there are two types of neurofibromatosis: types 1 and 2 (NF1 and NF2). NF1 and NF2 are caused by a change (or mutation) in the DNA of two different genes. People with NF1 and NF2 have very different medical problems. The common features shared by both types include neurofibromas (soft, non-cancerous tumors from nerves) and café-au-lait macules (coffee-colored skin spots). Today a doctor following special guidelines can usually figure out which type of NF a person has.

What is neurofibromatosis type 1?

Neurofibromatosis type 1 is a genetic disease that causes changes in the growth of nerves, skin and bones. It is found in about 1 in 3500 people. Both males and females can get NF1, and it affects people of all races and ethnicities. The disease usually starts in childhood. Over time a person with NF1 develops the benign (non-cancerous) nerve tumors (neurofibromas) that gives neurofibromatosis type 1 its name. People with NF1 also get other benign and malignant (cancer-causing) tumors, as well as unique changes in the coloration of their skin (freckling in the armpit and groin as well as coffee-colored spots called café-au-lait macules). More rarely, people with NF1 can also develop changes in their bones. This can lead to scoliosis (curving of the spine), pseudoarthosis (non-healing fractures, usually in the leg) and sphenoid wing dysplasia (changes in certain bones in the skull).

What causes NF1?

Neurofibromatosis type 1 is caused by an alteration (or mutation) in the DNA of the gene NF1, which makes the protein neurofibromin. A mutation in NF1 results in a non-working copy of the protein neurofibromin. The neurofibromin protein has many jobs in the body. One of its most important jobs is to help control the growth of cells. When neurofibromin doesn't work properly (from a mutation in the NF1 gene) growth of some cells is not under control and tumors from nerves (neurofibromas) and other places can form. Many of neurofibromin's other jobs are not well understood. For example, it is not clear to doctors how a mutation in the NF1 gene leads to the other features of neurofibromatosis type 1, such as learning disabilities or scoliosis.

What is the risk of having NF1 if another family member has NF1?

The only way to get neurofibromatosis type 1 is to have a change (mutation) in the NF1 gene. A mutation in the NF1 gene can be inherited from a parent ("run in the family") or appear for the first time in a family. A person with neurofibromatosis type 1 has a 50 percent chance of passing the change in the NF1 gene onto a child (regardless of gender) with each pregnancy. Even people with NF1 who are the first ones in the family affected have a 50% chance with each pregnancy of passing on the change in the NF1 gene. (This pattern is called autosomal dominant inheritance.) A person with a mutation in NF1 will always get the disease. This means that neurofibromatosis type 1 does not skip generations. If a child does not inherit the disease from an affected parent it means that the child has a very low chance (the same as the rest of the population) of having a child with neurofibromatosis type 1.

There are special exceptions to these rules. Genetic counseling is recommended to understand how these exceptions may apply to your family.

What do doctors do to take care of people with NF1?

The most important part of taking care of a person with NF1 is to make sure he/she really has NF1. Most of the time, the diagnosis can be made by a doctor following special rules (See Diagnostic Criteria for NF1). Sometimes the help of a geneticist (a doctor specializing in diseases caused by genes) is needed.

A person with NF1 should see a doctor with experience in NF1 every year. The doctor can be a pediatrician, internist, neurologist or geneticist. This way, problems can be better anticipated and managed. For children, the doctor will look for scoliosis (curving of the spine) and other problems with the bones. Plexiform neurofibromas (complex tumors involving many nerves) can grow and cause many problems in young people. Sometimes a visit to a specialist (like a surgeon) is needed to manage scoliosis or plexiform neurofibromas.

Learning disabilities are common in young people with NF1. A doctor can work with school officials to help develop a plan to help with learning. Yearly visits to an eye doctor can prevent rare tumors called optic pathway gliomas from causing problems with vision. Those same tumors can also cause growth problems and early puberty.

In adults, blood pressure should be checked yearly. Careful questioning is needed to monitor for possible changes in tumors. Changes like a loss of weight or appetite, increased pain or size of a tumor might mean a malignant tumor (cancer) is developing. People with NF1 can also develop rare problems with their arteries (the tubes that carry blood from the heart). The doctor can check for these symptoms by asking questions, performing a physical exam and ordering tests. People of all ages with NF1 have difficulties with the tumors (neurofibromas and plexiform neurofibromas) that are the most important feature of the disease. At this time there it is not possible to guess how many tumors a person will grow. Tumors can be removed by a surgeon in many different ways. There is unfortunately no medicine at this time that will prevent the growth of the tumors.

A person with NF1 has a 50 percent chance of passing the disease onto each child. A person with NF1 who desires to have a child has many choices to make. A genetic counselor and geneticist can help with these decisions.

Is there a cure for NF1?

Like many genetic diseases, there is no cure for NF1. There are several reasons for this. Remember that the disease is caused by a mutation (change) in the DNA of the gene NF1. The gene NF1 plays an important role in the growth and development of the human body. This is why so many organ systems (commonly, nerves, skin, bones, brain and eyes) are involved with the disease neurofibromatosis type 1.

Doctors and scientists have learned a lot about the importance of the gene NF1 from the mouse. Scientists have been able to change the DNA in one copy of the gene NF1 in the mouse. Not surprisingly, a mouse with one changed copy of NF1 develops some of the features of the human disease neurofibromatosis type 1. If both copies of the gene NF1 are changed, the mouse dies while still in the womb of its mother. The same is probably true for humans. NF1 is an important gene.

Curing neurofibromatosis type 1 requires "fixing" the changes in the NF1 gene in many of the cells of the body. This is the promise of gene therapy. Gene therapy has been used to "fix" genes on a small scale in some genetic diseases. At this time the technology does not exist to fix genes on the scale needed to cure neurofibromatosis type 1. Gene therapy may be considered as the "ultimate" cure for NF1 but is many years away from being routinely available.

For now, people with neurofibromatosis type 1 and doctors interested in the disease have some advantages. NF1 is a common problem and can help doctors and scientists understand more about nerve and cell growth. This means that there is a lot of interest in the disease. Cooperation between people with NF1 and doctors and scientists interested in NF1 has led to a much greater understanding of the disease and the problems it can cause. This has often allowed problems to be anticipated and managed.

To help develop new treatments, you may be able to enroll in a trial testing a new medication to treat neurofibromatosis type 1. Your doctor can help you determine if you are qualified to enroll.

What is neurofibromatosis type 2?

NF2 is much less common than NF1 and involves a different gene. It is found in about 1 in 50,000 people. It is also caused by a mutation (or change) in the DNA of a gene called NF2, which makes the protein merlin. Like neurofibromin (the changed protein in NF1), merlin also works to control the growth of nerves. People with NF2 usually get tumors of the nerve for hearing and balance. These tumors are called vestibular schwannomas. These tumors can cause deafness and problems with balance.

Changes in merlin also cause tumors of the brain, spine and skin. Some of these tumors are like those in NF1. This is why for many years it was difficult to sort out the differences between NF1 and NF2. In NF2 the type of mutation in merlin can often predict the seriousness of the disease. This is another difference with NF1, where that sort of prediction is not possible.