Neurofibromatosis Type 2 (NF2)

National Organization for Rare Disorders, Inc.

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It is possible that the main title of the report Neurofibromatosis Type 2 (NF2) is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • Bilateral Acoustic Neurofibromatosis
  • Central Form, Neurofibromatosis
  • Vestibular Schwannoma Neurofibromatosis
  • NF2

Disorder Subdivisions

  • None

General Discussion

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.

Affected Populations

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.

Standard Therapies

The diagnosis of NF2 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.

Investigational Therapies

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:

Diane Goetz

PTC Therapeutics, Inc.

(908) 912-9256

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:

Beth Miles-Markley

Research Assistant to Dr. Bradley Welling


Information on current clinical trials is posted on the Internet at 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

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 for more information.



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Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 101000; 6/3/99. Available at:


Children's Tumor Foundation

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Tel: (212)344-6633

Fax: (212)747-0004

Tel: (800)323-7938

TDD: (212)344-6633



Neurofibromatosis Network

213 S. Wheaton Ave.

Wheaton, IL 60187


Tel: (630)510-1115

Fax: (630)510-8508

Tel: (800)942-6825



Better Hearing Institute

1444 I Street NW

Suite 700

Washington, DC 20005

United States

Tel: (202)449-1100

Fax: (703)684-6048

Tel: (800)327-9355



National Association of the Deaf

8630 Fenton Street

Suite 820

Silver Springs, MD 20910


Tel: (301)587-1788

Fax: (301)587-1791

TDD: (301)587-1789



Cedars-Sinai Medical Genetics Institute

8700 Beverly Blvd

PACT Suite 400

Los Angeles, CA 90048


Tel: (310)423-9914

Fax: (310)423-2080

Tel: (800)233-2771


Children's National Medical Center

Genetics Department

Attn: Kenneth Rosenbaum MD

111 Michigan Ave. NW

Suite 1950

Washington, DC 20010

Tel: (202)476-2327

Tel: (888)884-2327



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981


Massachusetts General Hospital Neurofibromatosis Clinic

15 Parkman St. 8th Floor, Room 835

Boston, MA 02114


Tel: (617)724-7856

Fax: (617)724-8769



NF-2 Sharing Network

10074 Cabachon Court

Ellicott City, MD 21241

Tel: (410)461-2245

Fax: (410)461-2245

TDD: (410)461-5213

NIH/National Institute on Deafness and Other Communication Disorders

31 Center Drive, MSC 2320

Communication Avenue

Bethesda, MD 20892-3456

Tel: (301)402-0900

Fax: (301)907-8830

Tel: (800)241-1044

TDD: (800)241-1105



Comer Children's Hospital - University of Chicago (Neurofibromatosis Clinic)

Pediatric Neurology

5721 S. Maryland Avenue, MC3055

Chicago, IL 60637


Tel: (773)834-8064

Fax: (773)702-4786



Acoustic Neuroma Association of Canada

PO Box 193

Buckthorn, Ontario, KOL 1JO


Tel: 8005612622



BC Neurofibromatosis Foundation

Box 5339

Victoria, BC, V8R 6S4


Tel: 800385BCNF (2263)



Rare Cancer Alliance

1649 North Pacana Way

Green Valley, AZ 85614



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223


Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766



Let Them Hear Foundation

1900 University Avenue, Suite 101

East Palo Alto, CA 94303

Tel: (650)462-3174

Fax: (650)462-3144



Alberta Neurofibromatosis Association

636 Hunterfield Place NW


Alberta, T2K 4L6


Tel: 4032754894

Tel: 8669392263

Email: or


American Academy of Audiology

11730 Plaza America Drive, Suite 300

Reston, VA 20190

Tel: (703)790-8466

Fax: (703)790-8631

Tel: (800)222-2336




American Society of Clinical Oncology

2318 Mill Road Suite 800

Alexandria, VA 22314

Tel: (571)483-1780

Fax: (571)366-9537

Tel: (888)651-3038



Hearing Loss Association of America

7910 Woodmont Avenue

Suite 1200

Bethesda, MD 20814

Tel: (301)657-2248

Fax: (301)913-9413



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see