$Unique_ID{BRK04042} $Pretitle{} $Title{Neurofibromatosis} $Subject{Bilateral Acoustic Neurofibromatosis (NF 2) Central Neurofibromatosis (NF 2) Intestinal Neurofibromatosis Elephant Man Disease Mixed central and Peripheral Neurofibromas Neurofibroma, multiple Neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome NF NF 1 Recklinghausen's Phakomatosis also known as Phakomatosis Recklinghausen RF 1 Von Recklinghausen Disease, also known as Recklinghausen's I and Recklinghausen Disease} $Volume{} $Log{} Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1993 National Organization for Rare Disorders, Inc. 3: Neurofibromatosis ** IMPORTANT ** It is possible the main title of the article (Neurofibromatosis) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names and disorder subdivisions covered by this article. Synonyms Bilateral Acoustic Neurofibromatosis (NF 2) Central Neurofibromatosis (NF 2) Intestinal Neurofibromatosis Elephant Man Disease Mixed central and Peripheral Neurofibromas Neurofibroma, multiple Neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome NF NF 1 Recklinghausen's Phakomatosis also known as Phakomatosis Recklinghausen (RF 1) Von Recklinghausen Disease, also known as Recklinghausen's I and Recklinghausen Disease DISORDER SUBDIVISIONS NF 1 NF 2 Information on the following diseases can be found in the Related Disorders section of this report: Acoustic Neuroma McCune-Albright Syndrome Proteus Syndrome Tuberous Sclerosis General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Neurofibromatosis is a term used to describe what are now known to be two distinctly different disorders: The more common type 1 neurofibromatosis (NF 1), and the less common type 2 (NF 2). Both disorders are inherited through autosomal dominant genes, but the genes involved are on separate chromosomes. Major symptoms include numerous benign tumors (neurofibromas) and discolored spots on the skin. NF 2 causes hearing impairment as well as other symptoms. Symptoms Both types of Neurofibromatosis are characterized by the occurrence of multiple benign (noncancerous) tumors, arising most frequently from the peripheral nervous system. These tumors (neurofibromas) appear on or under the skin or in deeper areas within the body. Symptoms of NF 1 usually appear during childhood. The disease is progressive and tends to become more active at puberty and during pregnancy, although the course and symptoms of NF vary and are unpredictable. Brown spots (cafe-au-lait) on the skin are usually the first sign. These spots measure approximately 0.5 cm in diameter in children and grow to 1.5 cm in diameter in adults. Six or more cafe-au-lait spots (macules) and two or more neurofibromas (tumors) are diagnostic in a child. Freckling under the arm (axillary) or in the area of the groin (inguinal), or two or more small grayish neuromas in the iris of the eye (Lisch nodules) are important diagnostic criteria. Tumors (neurofibromas) occur in NF 1 and can form under the skin or in deeper areas in the body. Pain may or may not occur. Tumors can produce disfigurement and orthopedic problems, including curvature in the spine (scoliosis) and bone loss on the weight bearing long bones of the body (pseudoarthrosis). This can result in the bending or even the fracture of these bones. Sexual development may be delayed or early (precocious) and learning disabilities may occur. Optic tumors (glioma), local or widespread benign tumor-like nodules (hamartomas), and other central nervous system lesions are common. NF 2 develops later than NF 1, usually during the teens or 20's. Fewer cafe-au-lait spots and skin (cutaneous) neurofibromas develop. NF 2 is characterized by progressively enlarging benign tumors in both auditory canals (bilateral acoustic neuromas). It may also be associated with brain and spinal cord tumors. Buzzing and ringing in the ears and eventual loss of hearing occur as result of these neuromas. Causes NF 1 and NF 2 are inherited as autosomal dominant traits; however, about half of all cases are due to new mutations that are not inherited from parents. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, 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 normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. The gene for NF 1 is on chromosome 17 (17q11.2). The gene for NF 2 is on chromosome 22 (22q). The NF2 gene is a new type of tumor suppressor gene that has been associated with the non-inherited as well as inherited forms of cancer. Neurofibromatosis 2 results when the gene is activated. This same gene is also implicated in approximately thirty percent of brain tumors that occur sporadically. The NF2 gene produces a protein termed "merlin" that is an acronym for moesin-ezrin-radaxin-like-protein. These proteins are thought to act like links between proteins in the cell membrane, that hold cells together, and the cytoskeleton, a lattice-work of tiny filaments that act to support the cell. A localized form of neurofibromatosis appears to be caused by a somatic mutation, with little risk of recurrence in offspring. Affected Population Neurofibromatosis affects approximately 100,000 Americans, both male and female. It is estimated that NF 1 affects 1:4,000 individuals; NF 2 affects 1:50,000. Related Disorders Symptoms of the following disorders can be similar to those of Neurofibromatosis. Comparisons may be useful for a differential diagnosis: Acoustic Neuroma is a benign tumor (neuroma) of the 8th cranial nerve. This nerve lies within the internal auditory canal. Symptoms of this disorder include ringing in the ears (tinnitus), hearing loss, or both. The tumor may grow in the direction of the brain stem. Increasing pressure inside the brain may led to personality changes and impaired thinking. As pressure increases on the facial nerve, facial twitching can occur. (For more information on this disorder, choose "Acoustic Neuroma" as your search term in the Rare Disease Database). McCune-Albright Syndrome is a multi-system disorder primarily characterized by abnormal fibrous tissue development (dysplasia) in one or more bones, abnormally early puberty, and brown (cafe-au-lait) spots on the skin. Other symptoms may include an overactive thyroid gland (hyperthyroidism), other endocrine abnormalities, and a variety of bone and soft-tissue tumors. (For more information on this disorder, choose "McCune- Albright" as your search term in the Rare Disease Database). Proteus syndrome is a rare hereditary disorder characterized by abnormal and asymmetric growth. Diverse abnormalities of the skin, face, eyes, ears, lungs, muscles and nerves are present. The symptoms of this disorder become apparent during the first year of life. Skin lesions may occur as well as hemangiomas, lipomas and lymphangiomas. Abnormal growths in the abdominal cavity may occur as well. It was once believed that the broadway show, "The Elephant Man", was based on a person with neurofibromatosis, but it was later discovered that this patient actually had Proteus syndrome. (For more information on this disorder, choose "Proteus Syndrome" as your search term in the Rare Disease Database). Tuberous Sclerosis is a rare disorder characterized by seizures, mental retardation, developmental delay, lesions of the eyes and skin and brain tumors. Seizures, which occur in 90 percent of patients, are often the first symptoms. Abnormalities may be seen on an electroencephalograph (EEG). Approximately 60 to 90 percent of infants have brownish skin spots (hypomelanotic macules) at birth. Fibromas may present on the area around or under the nails (periungual or subungual). (For more information on this disorder, choose "Tuberous Sclerosis" as your search term in the Rare Disease Database). Therapies: Standard Surgical removal of troublesome Neurofibromatosis tumors may be beneficial when they cause discomfort. Physical therapy is occasionally useful and orthopedic devices can improve disabilities in some cases. Other treatment is symptomatic and supportive. Therapies: Investigational Neurofibromatosis research is ongoing in numerous areas including recombinant DNA and nerve growth factor to understand the formation of neurofibromas. Recent genetic studies have led to the development of genetic tests. Once the gene that causes NF 1 and NF 2 can be cloned, research on prevention and new treatments will be pursued. Research Projects: Families with one or more members who have central Neurofibromatosis (NF II) with Bilateral Acoustic Neuromas are being sought for a clinical research study at the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, MD. The goal of the study is to establish methods for early detection and diagnosis of this type of Neurofibromatosis. Doctors who wish to refer potential candidates or obtain additional information should contact: Dr. Donald Wright Surgical Neurology Branch NINCDS, Bldg. 10A, Rm. 3E68 Bethesda, MD 20892 (301) 496-2921 Researchers are studying learning disabilities and neurological changes in NF children aged birth to eighteen years. A controlled study is underway among children with NF along with siblings who do not have the disorder. Testing is being performed in conjunction with Children's Hospital, Washington, DC. Neurofibromatosis Clinic Children's Hospital 111 Michigan Avenue, NW Washington, DC 20010 (202) 745-2187 Ongoing research is directed toward understanding the genetic changes in tumor formation in Neurofibromatosis. Tissue is requested from any known or suspected malignancy. Samples of neurofibromas from female patients is also requested. Understanding of the genetic basis of tumor formation represents a major step toward a improved diagnosis and treatment of this disorder. Patients undergoing such surgery should contact: Dr. Gary R. Skuse or Dr. Peter T. Rowley University of Rochester Medical Center Division of Genetics Box 641 601 Elmwood Ave. Rochester, NY 14642 (716) 275-3461 This disease entry is based upon medical information available through May 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Neurofibromatosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Neurofibromatosis, Inc. 3401 Woodridge Ct. Mitchellville, MD 20716 (301) 577-8984 National Neurofibromatosis Foundation, Inc. 141 Fifth Ave. New York, NY 10010 (212) 460-8980 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 For information on genetics and genetic counseling referrals, please contact: Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 March of Dimes Birth Defects Foundation 1275 Mamaroneck Ave. White Plains, NY 10605 (914) 428-7100 CLINICAL FACILITIES Massachusetts General Hospital Neurofibromatosis Clinic Department of Neurosurgery 15 Parkman St., Room 312 Boston, MA (617) 726-3776 Att: Robert Marthuza, MD Children's Hospital Neurofibromatosis Clinic 111 Michigan Avenue, NW Washington, DC 20010 (202) 745-2187 Att: Kenneth Rosenbaum, MD Children's Hospital Neurofibromatosis Clinic 34th and Civic Center Blvd., Room 9028 Philadelphia, PA (215) 596-9645 Att: Anna Meadows, MD Baylor College of Medicine Neurofibromatosis Clinic 1 Baylor Plaza Houston, Texas 77030 (713) 799-6103 Att: Vincent Riccardi, MD Mount Sinai School of Medicine Neurofibromatosis Clinic 100th St. and Madison Ave. New York, NY (212) 650-6500 Att: Alan Rubinstein, MD References BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 1233-34. CLINICAL REVIEW OF NEUROFIBROMATOSIS, J. Rosner; J Am Optom Assoc (August, 1990, Issue 61 (8)). Pp. 613-618. LISCH NODULES IN NEUROFIBROMATOSIS TYPE I, Marie-Louise E. Lubs, et al.; N Eng J. Med., (May 2, 1991, issue 324 (24)). Pp. 1264-1266.