Neurofibromatosis type 2

Synonyms

7

Overview

Neurofibromatosis type 2 is a disorder characterized by the growth of noncancerous tumors in the nervous system. The most common tumors associated with neurofibromatosis type 2 are called vestibular schwannomas or acoustic neuromas. These growths develop along the nerve that carries information from the inner ear to the brain (the auditory nerve). Tumors that occur on other nerves are also commonly found with this condition.

Almost all people affected by NF2 develop bilateral (affecting both sides) vestibular schwannomas by age 30 years; however, other tumors of the central nervous system (the brain and spinal cord) are common, as well.

The signs and symptoms of neurofibromatosis type 2 usually appear during adolescence or in a person's early twenties, although they can begin at any age. The most frequent early symptoms of vestibular schwannomas are hearing loss, ringing in the ears (tinnitus), and problems with balance. In most cases, these tumors occur in both ears by age 30. If tumors develop elsewhere in the nervous system, signs and symptoms vary according to their location. Complications of tumor growth can include changes in vision, numbness or weakness in the arms or legs, and fluid buildup in the brain. Some people with neurofibromatosis type 2 also develop clouding of the lens (cataracts) in one or both eyes, often beginning in childhood.

The criteria that were chosen for the diagnosis of NF2 were the following, of which only 1 criterion was needed to make the diagnosis:

  • Bilateral CN VIII masses seen with appropriate imaging techniques (eg, computed tomography [CT] scanning or magnetic resonance imaging [MRI])
  • A first-degree relative with NF2 and either a unilateral CN VIII mass or 2 of the following:
  • Neurofibroma
  • Meningioma
  • Glioma
  • Schwannoma
  • Juvenile posterior subcapsular lenticular opacity

In the past 2 decades, a revision to these diagnostic criteria of NF2 was proposed that concerns the addition of a section for presumptive or probable diagnosis of NF2. These modified criteria are listed as follows:

  • Definite diagnosis of NF2
  • Bilateral CN VIII schwannomas on MRI or CT scan (no biopsy necessary)
  • First-degree relative with NF2 and either unilateral early-onset CN VIII schwannoma (age 2) and unilateral CN VIII schwannoma or 1 of the following:
  • Glioma
  • Schwannoma
  • Juvenile posterior subcapsular lenticular opacity

Symptoms

On average, the signs and symptoms associated with neurofibromatosis type 2 (NF2) begin to develop in the late teens or early twenties. Almost all people affected by NF2 develop bilateral (affecting both sides) vestibular schwannomas by age 30 years. These benign tumors, which are also called acoustic neuromas, may cause tinnitus, hearing loss, and/or balance dysfunction. Other tumors of the central nervous system (brain and spinal cord) are also commonly found with this condition. The signs and symptoms of NF2 vary from person to person and generally depend on the size, location and number of tumors. For example, complications of tumor growth may include changes in vision; numbness or weakness in the arms or legs; fluid buildup in the brain; and/or seizures.

People with NF2 may also develop cataracts in one or both eyes, often beginning in childhood. Cataracts often lead to decreased vision and other visual impairments (i.e. double vision, loss of color intensity, and/or seeing halos around light).

Causes

Neurofibromatosis type 2 is caused by changes (mutations) in the NF2 gene. NF2 is a tumor suppressor gene, which means that it encodes a protein that stops cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in NF2 result in an abnormal protein that is unable to carry out its normal role. This contributes to the development of the many different types of tumors found in neurofibromatosis type 2.

People with neurofibromatosis type 2 are typically born with one mutated copy of the NF2 gene in each cell and are, therefore, genetically predisposed to develop the tumors associated with the condition. For a tumor to form, two copies of the NF2 gene must be altered. The mutation in the second copy of the NF2 gene is considered a somatic mutation because it occurs during a person's lifetime and is not inherited. Almost everyone who is born with one NF2 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is inherited in an autosomal dominant manner. This means that a person only needs a change (mutation) in one copy of the responsible gene in each cell to have a genetic predisposition to the tumors associated with NF2. In approximately half of cases, an affected person inherits the mutation from an affected parent. Other cases may result from new (de novo) mutations in the gene; these cases occur in people with no history of the disorder in their family. A person with NF2 has a 50% chance with each pregnancy of passing along the altered gene to his or her child.

Diagnosis

The diagnosis of neurofibromatosis type 2 (NF2) is usually based on the presence of characteristic signs and symptoms. Genetic testing for a change (mutation) in the NF2 gene is available; however, this testing may not be informative in all people affected by NF2, particularly those who are mosaic for the condition.

Prognosis

The long-term outlook (prognosis) for people with neurofibromatosis type 2 (NF2) varies based on a number of factors, including the age at which symptoms develop; the degree of hearing deficit; and the number and location of various tumors. On average, people affected by NF2 begin showing symptoms of the condition in their late teens to early twenties (onset range: birth to 70 years) and almost all affected people develop bilateral (affecting both sides) vestibular schwannomas by age 30 years. The size, location, and number of tumors can vary significantly from person to person. Although the tumors associated with NF2 are generally benign, they can interfere with quality of life and lead to early mortality due to their location and quantity. The average age of death in people with NF2 is 36 years. However, survival is improving with earlier diagnosis and better treatment in specialty centers.

Treatment

People with neurofibromatosis type 2 (NF2) are generally monitored periodically for the development of associated tumors and other health problems. This may include an MRI of the brain and spinal cord; hearing and speech evaluations; and an eye exam.

The treatment of NF2 depends on the signs and symptoms present in each person. For example, vestibular schwannomas are typically slow-growing tumors so they may be observed for a period of time before treatment becomes necessary. When they begin to cause symptoms, vestibular schwannomas are usually treated with surgery and less frequently, with radiation therapy. Other tumors associated with NF2 are also treated surgically, although chemotherapy and/or radiation therapy may also be recommended in rare circumstances.

Hearing preservation and augmentation are also important in the management of people with NF2.

Resources

  • NIH
  • Mayo Clinic
  • Genetics Home Reference