Neurofibromatosis Type 1
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What is neurofibromatosis type 1?
Neurofibromatosis type 1 is a genetic condition characterized by skin pigment changes and tumors that grow along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.
Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple cafe-au-lait spots, which are flat patches on the skin that are the color of coffee with milk. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.
Most adults with neurofibromatosis type 1 have neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and leukemia (cancer of blood-forming tissue).
During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (the iris). Lisch nodules do not interfere with vision. Another type of tumor, called an optic glioma, can occur on the nerve leading from the eye to the brain. These tumors are usually benign, but can cause reduced vision or total vision loss.
Additional signs and symptoms of neurofibromatosis type 1 include high blood pressure and skeletal abnormalities such as curvature of the spine (scoliosis). Most people with this condition have normal intelligence. Fewer than 10 percent are mentally retarded, but about half of affected children have learning disabilities.
In some cases, people have features of both neurofibromatosis type 1 and another genetic condition, Noonan syndrome. Noonan syndrome is characterized by distinctive facial features, short stature, heart defects, and skeletal abnormalities. The combination of signs and symptoms of these two conditions is sometimes called neurofibromatosis-Noonan syndrome. Other affected individuals have features of neurofibromatosis type 1 with developmental delay and a heart defect called pulmonic stenosis. Together, these signs and symptoms are known as Watson syndrome. Researchers believe that neurofibromatosis-Noonan syndrome and Watson syndrome are variants of neurofibromatosis type 1 because the conditions are usually caused by mutations in the same gene.
How common is neurofibromatosis type 1?
Neurofibromatosis type 1 occurs in 1 in 3,000 to 4,000 people.
What genes are related to neurofibromatosis type 1?
Mutations in the NF1 gene cause neurofibromatosis type 1.
The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in nerve cells and in specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 gene lead to the production of a nonfunctional version of neurofibromin that cannot regulate cell growth and division. As a result, tumors such as neurofibromas can form along nerves throughout the body. Researchers are not yet certain how mutations in the NF1 gene cause other features of neurofibromatosis type 1, such as cafe-au-lait spots.
How do people inherit neurofibromatosis type 1?
Neurofibromatosis type 1 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the NF1 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases are the result of new mutations in the NF1 gene, and occur in people with no history of the disorder in their family.
Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1. A mutation in the second copy of the NF1 gene occurs during a person's lifetime in specialized cells surrounding nerves. Almost everyone who is born with one NF1 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 1.
Source: National Institutes of Health
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Investigators at University of Freiburg target multiple endocrine neoplasia
2009 JUL 20 - (NewsRx.com) -- "Head and neck paragangliomas (HNPs) occur as sporadic or familial entities, the latter mostly in association with germline mutations of the SDHB, SDHC, or SDHD(SDHx) genes. Heritable non-SDHx HNP might occur in von Hippel-Lindau disease (VHL, VHL gene), multiple endocrine neoplasia type 2 (MEN2, RET gene), and neurofibromatosis type 1 (NF1, NF1 gene)," researchers in Freiburg, Germany report. "Reports of non-SDHx HNP presentations are scarce and guidance for genetic testing nonexistent. An international consortium registered patients with HNPs and performed mutation analyses of the SDHx, VHL, and RET genes. Those with SDHx germline mutations were excluded for purposes of this study. Personal and family histories were evaluated for paraganglial tumors, for the major tumor manifestations, and for family history of VHL, MEN2, or NF1. Twelve patients were found to have hereditary non-SDHx HNPs of a total of 809 HNP and 2084 VHL registrants, 11 in the setting of germline VHL mutations and one of a RET mutation. The prevalence of hereditary HNP is five in 1000 VHL patients and nine in 1000 non-SDHx HNP patients. Comprehensive literature review revealed previous reports of HNP sin five VHL, two MEN2, and one NF1 patient. Overall, 11 here presented HNP cases, and four previously reported VHL-HNPs had lesions characteristic for VHL and/or a positive family history for VHL," wrote C.C. Boedeker and colleagues, University of Freiburg. The researchers concluded: "Our observations provide evidence that molecular genetic testing for VHL or RET germline mutations in patients with HNP should be done only if personal and/or family history shows evidence for one of these syndromes. (J Clin Endocrinol Metab 94: 1938-1944, 2009)." Boedeker and colleagues published their study in the Journal of Clinical Endocrinology & Metabolism (Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2. Journal of Clinical Endocrinology & Metabolism, 2009;94(6):1938-1944). For additional information, contact H.P.H. Neumann, University of Freiburg, Dept. of Nephrology & General Medical, Hugstetter Str 55, D-79106 Freiburg, Germany. Publisher contact information for the Journal of Clinical Endocrinology & Metabolism is: Endocrine Society, 8401 Connecticut Avenue, Suite 900, Chevy Chase, MD 20815-5817, USA. Keywords: Germany, Freiburg, Clinical Endocrinology, Endocrinology, Genetics, Hippel-Lindau Disease, Metabolism, Multiple Endocrine Neoplasia, Neurofibromatoses, Neurofibromatosis, Paraganglioma, University of Freiburg. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2009, Pain & Central Nervous System Week via NewsRx.com.
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