Article: Neurofibromatosis

What is neurofibromatosis?

Neurofibromatosis is a condition in which noncancerous tumors called neurofibromas grow along nerves in the skin, brain, and other parts of the body. The two main types of neurofibromatosis can be distinguished by the locations of the tumors and by genetic testing.

Genetic changes are related to the following types of neurofibromatosis.

• neurofibromatosis 1
• neurofibromatosis 2

The features of neurofibromatosis depend on where the tumors are located and differ for each type of the condition. Sometimes the signs and symptoms are so mild that individuals may be unaware of having this disorder. In other cases, signs and symptoms can be very serious or life-threatening. For a discussion of specific features, please refer to the summaries for neurofibromatosis 1 and neurofibromatosis 2.

How common is neurofibromatosis?

Neurofibromatosis 1 is more common than neurofibromatosis 2. In the United States, neurofibromatosis 1 affects about 1 in 3,000 births, and neurofibromatosis 2 occurs in about 1 in 40,000 births.

What genes are related to neurofibromatosis?

Mutations in the NF1 and NF2 genes cause neurofibromatosis.

The NF1 and NF2 genes make proteins found in nerve cells and in specialized cells that surround the nerves. The proteins act as tumor suppressors, which means that they normally keep cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 or NF2 gene lead to a nonfunctional protein that cannot regulate cell growth and division, allowing multiple noncancerous tumors to form.

How do people inherit neurofibromatosis?

Neurofibromatosis is considered to have an autosomal dominant pattern of inheritance because affected people may have affected relatives in successive generations (such as parents and children). Unlike other autosomal dominant conditions, however, two copies (instead of one copy) of the NF1 or NF2 gene must be altered before the condition's characteristic features will develop. People with neurofibromatosis are born with one mutated copy of the gene in each cell. Then, during their lifetime, a second mutation occurs in the other copy of the gene in nerve cells or specialized cells surrounding nerves, triggering tumor formation. Almost everyone who is born with one NF1 or NF2 mutation acquires a second mutation in many cells during their lifetime and develops the signs and symptoms of neurofibromatosis.

Not all cases of neurofibromatosis are inherited from an affected parent. In about half the cases, there is no family history of the condition. Instead, a new mutation occurs during fetal development or in the reproductive cells (sperm and eggs) of unaffected parents. People born with a new mutation in the NF1 or NF2 gene can pass on this mutation to their children.