Neurofibromatosis type 2 (NF2) is a rare genetic disorder that is primarily characterized by benign (noncancerous) tumors of the nerves that transmit sound impulses from the inner ears to the brain (bilateral acoustic neuromas vestibular schwannomas). Associated symptoms and findings may become evident during childhood, adolescence, or early adulthood. Depending on the exact location and size of the acoustic neuromas/vestibular schwannomas, such findings may include disturbances of balance and walking (gait); dizziness; headache; facial weakness, numbness, or pain; ringing in the ears (tinnitus); and/or progressive hearing loss.
In some individuals with NF2, additional abnormalities may also be present. These may include loss of transparency of the lenses of the eyes (juvenile posterior subcapsular opacities), progressive visual impairment, or an increased risk of developing certain tumors of the brain and spinal cord (central nervous system).
NF2 results from changes (mutations) of a gene on the long arm (q) of chromosome 22 (22q12.2). The NF2 gene regulates the production of a protein that functions as a tumor suppressor. In some individuals with NF2, the disorder is caused by new (sporadic) mutations of the gene that occur for unknown reasons. In other affected individuals, NF2 is inherited as an autosomal dominant trait.
The term "neurofibromatosis" is sometimes also used to describe a second, distinct form of NF known as neurofibromatosis type I (NF1). More common than NF2, NF1 is primarily characterized by the development of multiple noncancerous (benign) tumors of nerves and skin (neurofibromas) and areas of abnormally decreased or increased coloration (hypo- or hyperpigmentation) of the skin, such as pale tan or light brown discolorations (cafe-au-lait spots) on the skin of the trunk or other regions. In contrast, in individuals with NF2, benign fibrous tumors of the skin (cutaneous neurofibromas) and areas of abnormal pigmentation are considered relatively rare. As with NF2, NF1 may be inherited as an autosomal dominant trait or appear to occur randomly due to new (sporadic) genetic changes.
The characteristic symptoms of neurofibromatosis type 2 usually develop around the time of puberty or during early adulthood. These may include balance problems, buzzing or ringing in the ears (tinnitus), and/or gradual hearing loss. These symptoms usually result from the presence of benign tumors on both auditory nerves (acoustic neuromas vestibular schwannomas). Other tumors of the central nervous system may also develop including neurofibromas, meningiomas, gliomas, and schwannomas. Benign tumors may also occur on the spinal cord. (For more information on tinnitus, choose “tinnitus” as your search term in the Rare Disease Database.)
Individuals with neurofibromatosis type 2 may also develop cloudiness on the lenses of the eyes (posterior capsular cataracts) at a younger age than would otherwise be expected. Symptoms of cataracts may include impaired vision, and in some cases the progressive loss of vision. (For more information on this disorder, choose “cataracts” as your search term in the Rare Disease Database.)
People with neurofibromatosis type 2 generally have fewer brown spots (cafe-au-lait) on the skin than those who have neurofibromatosis type 1. Affected individuals may also experience spasms of the facial muscles; generalized muscle weakness, numbness, pain, and/or partial paralysis; difficulty swallowing; and/or impaired speech. Other neurological problems may also develop including headaches and/or seizures.
In some individuals with NF2, the disorder is inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
In other individuals with NF2, there is no family history of the disease. In such cases, NF2 is caused by new (sporadic) genetic changes (mutations) that appear to occur randomly for unknown reasons.
NF2 results from mutations of a gene located on the long arm of chromosome 22 (22q12.2). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered.
The NF2 gene regulates (encodes for) the production of a protein known as merlin/schwannomin that plays a role in suppressing the development of certain tumors (tumor suppressor). According to investigators, merlin/schwannomin is related to a class of proteins (ezrin-radixin-moesin proteins) that serve to link the internal, supportive system within a cell (cytoskeleton) to proteins in cell membranes. Several different mutations of the NF2 gene have been identified in individuals with the disorder (e.g., deletions, nonsense and frameshift mutations). Investigators suggest that different mutations of the gene may contribute to the wide variability of symptoms and findings in affected individuals.
NF2 is a rare disorder that affects males and females in equal numbers. All races and ethnic groups are affected by this disorder. The estimated incidence of neurofibromatosis type 2 is 1 in 40,000 people. The symptoms of this disease typically become obvious during puberty or early adulthood.
The diagnosis of NF. is confirmed by a thorough clinical evaluation and specialized testing (i.e., CT scan, magnetic resonance imaging (MRI), pneumoencephalogram, or arteriogram).
The treatment of acoustic neuromas associated with NF2 is the surgical removal of the tumors, when possible. The surgical procedure that is performed is based upon the size and precise location of the tumors. Radiation therapy may be considered for some individuals with this disorder, especially those who are not candidates for surgery. Other treatment is symptomatic and supportive.
Genetic counseling will be of benefit for people with NF2 and their families.
On July 27, 2009 – PTC Therapeutics, Inc. (PTC) announced the initiation of a Phase 2 clinical trial of PTC299 in adult patients with NF2. PTC299 is a novel, orally administered investigational new drug that is designed to selectively block tumor-related vascular endothelial growth factor (VEGF). With its novel mechanism of action, PTC299 has the potential to meet significant unmet medical need in NF2 and other conditions resulting from the over-expression of VEGF.
For additional information contact:
PTC Therapeutics, Inc.
The Ohio State University Department of Otolaryngology-Head and Neck Surgery is currently (2009) conducting a study to determine the frequency of birth defects and miscarriages in patients with NF2 and to investigate the frequency of color blindness in NF2 patients. Individuals over 18 with NF2 are eligible to participate.
To enroll in the study and to receive a study packet contact:
Research Assistant to Dr. Bradley Welling
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For more information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruiting Office:
Tollfree: (800) 411-1222
TTY: (866) 411- 1010
For information about clinical trials sponsored by private sources, contact:
Information about current clinical trials is also available from Neurofibromatosis, Inc. at http://www.nfinc.org
The Children’s Tumor Foundation launched an NF Registry in 2012. The purpose of this registry is to find people who may be eligible for clinical trials or other research studies being conducted in the field of NF, and to determine the commonality of specific NF characteristics. Please go to www.nfregistry.org for more information.
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