Neurofibromatosis type II

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at October 29, 2016
StartDiseasesNeurofibromatosis type II

Neurofibromatosis type II is a genetic disorder that can be either inherited or arise from de novo mutations. It is caused by mutations in a gene located on chromosome 22 that is responsible for making the protein that plays a role in tumor suppression. NF2, as it is also known, strikes roughly 1 in 25,000 people. There is no prevention or cure for this disease, but it can be managed with proper treatment and monitoring.

Contents

Definition & Facts

There are three distinct types of neurofibromatosis: neurofibromatosis type I, neurofibromatosis type II, and schwannomatosis. Neurofibromatosis type II is considerably less common than type I, and involves the development of benign tumors in both the central nervous system and peripheral nervous systems. Schwannomatosis does not cause neurofibromas and is caused by different kinds of genetic mutations than neurofibromatosis type I or neurofibromatosis type II. It involves the presence of schwannomas which are tumors in Schwann cells.

Tumors that are most commonly seen among those with neurofibromatosis type II are acoustic neuromas which grow on the vestibulocochlear nerve, the nerve which transmits information regarding sound and balance between the inner ear and the brain. Tumors are generally removed by surgery.

Symptoms of NF2 typically arise in late adolescence or early twenties, although symptoms may not appear until age 40 or even 50. The survival rate is increasing with better awareness, better molecular genetic testing, and better treatments. A mere twenty years ago the average age at death was 36 for individuals with NF2; today people with NF2 are surviving longer. Recent studies, however, associate an earlier age of onset of NF2 with a higher mortality rate.

Symptoms & Complaints

The primary symptoms of neurofibromatosis type II are benign tumors that form on the nerves responsible for transmitting sound and balance to the brain. Common complaints include tinnitus and hearing loss, but depending on the size and location of the tumors, one may experience the following symptoms as well:

Less common symptoms include cataracts at an earlier than average age, increased risk for developing tumors of the brain lining and spinal cord, and vision loss/visual impairment. Almost all individuals with neurofibromatosis type II exhibit tumors (also called acoustic neuromas) on the vestibulocochlear nerve by the time they are 30.

Symptoms may appear in childhood, but they are often subtle and ignored unless there is already a family history of NF2 present. Unless a diagnostic image is taken and reveals the presence of tumors, NF2 can go undiagnosed.

Causes

Neurofibromatosis type II is caused by a mutation in the gene on the NF2 gene that is responsible for producing merlin, a protein that acts as a tumor suppressor. The protein merlin also acts as a link between the internal systems of a cell to the cell membrane.

Neurofibromatosis type II is an autosomal dominant genetic disorder, meaning that a single copy of the abnormal gene can cause the disorder. However, half of all cases arise as a result of de novo mutations in which the patient has no family history of the condition.

Diagnosis & Tests

Diagnosing neurofibromatosis type II involves a thorough clinical exam, including computed tomography (CT) scans and magnetic resonance imaging (MRI) scans to determine the size and location of tumors. The presence of tumors on one or both vestibulocochlear nerves is the most common factor used in an initial diagnosis; other factors used are the presence of multiple tumors in the lining of the brain and family history. Genetic testing at the molecular level is possible to determine if the NF2 gene is affected by mutations.

Those who have been diagnosed with this condition should have regular hearing examinations and vision examinations to assess any hearing loss, vision loss, or the appearance of cataracts. Annual MRIs are used to monitor the body for either new or current tumors, especially if the tumors are located in the brain, brainstem, or spinal cord. 

Treatment & Therapy

The most common treatment for neurofibromatosis type II is the surgical removal of the tumors, especially those residing on the auditory nerve. Surgery can also correct the cataracts and retinal abnormalities associated with NF2, and cochlear implants can be used to combat any hearing loss resulting from damage to the auditory nerve.

Individuals who are not candidates for surgery typically receive radiation if the tumor(s) is located in an area which may not be best served by surgical techniques. Therapy with a VEGF (vascular endothelial growth factor) inhibitor is also used; these inhibitors (such as bevacizumab) prevent the tumors from growing by blocking the formation of blood vessels in the tumors.

Prevention & Prophylaxis

There is no prevention and no cure for neurofibromatosis type II. If an individual is concerned about the possibility of passing on the gene to their children, they can opt to partake in genetic testing in order to assess their risk.

Once a diagnosis has been made, annual follow-ups are strongly encouraged to monitor the growth of tumors, especially those affecting the areas of the brain and spinal cord, as tumors may grow large enough to cause compression of the brainstem.