April 28, 2008
Years published: 2000, 2003
Turcot syndrome is a rare inherited disorder characterized by the association of benign growths (adenomatous polyps) in the mucous lining of the gastrointestinal tract with tumors of the central nervous system. Symptoms associated with polyp formation may include diarrhea, bleeding from the end portion of the large intestine (rectum), fatigue, abdominal pain, and weight loss. Affected individuals may also experience neurological symptoms, depending upon the type, size and location of the associated brain tumor. Some researchers believe that Turcot syndrome is a variant of familial adenomatous polyposis. Others believe that it is a separate disorder. The exact cause of Turcot syndrome is not known.
Turcot syndrome is characterized by the formation of multiple benign growths (polyps) in the colon that occur in association with a primary brain tumor. These growths are associated with bleeding from the rectum, diarrhea, constipation, abdominal pain, and/or weight loss. The number and size of these polyps may vary greatly from case to case, ranging from fewer than 10 to more than 100.
Some researchers have separated Turcot syndrome into two forms. type 1 is characterized by the presence of fewer than 100 colonic polyps. These polyps are large in size and more likely to become malignant (cancerous). Type 2 is characterized by smaller, more numerous colonic polyps. This type of Turcot syndrome closely resembles familial adenomatous polyposis. (For more information on familial adenomatous polyposis, see the Related Disorders section of this report.)
Individuals with Turcot syndrome often have neurological abnormalities that vary, depending upon the type, size, and location of the associated brain tumor. In cases of Turcot syndrome, the brain tumor is often a glioma. Additional brain tumors that have been associated with Turcot syndrome include medulloblastomas, glioblastomas, ependymomas, and astrocytomas. Medulloblastomas occur with greater frequency in the type 2 form of Turcot syndrome.
Individuals with Turcot syndrome have a much greater risk than the general population of developing colon cancer later in life. Affected individuals also have a predisposition to develop malignant (cancerous) tumors in areas outside the colon, including thyroid, adrenal, and/or abdominal tumors.
Additional symptoms associated with Turcot syndrome include small, coffee-colored spots on the skin (cafe-au-lait spots), the formation of multiple, benign fatty tumors (lipomas), and/or the development of a type of skin cancer known as basal cell carcinoma. Basal cell carcinoma is characterized by the formation of small, shiny, firm masses of tissues (nodules); flat, scar-like lesions (plaques); or red patches covered by thick, dry, silvery scales on the skin.
Recent research indicates that one type of Turcot syndrome is inherited as an autosomal recessive trait and the other as an autosomal dominant trait.
Turcot syndrome type 1, sometimes called “true” Turcot syndrome, is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
Researchers believe that mutations to two DNA mismatch repair genes (i.e., MLH1 and PMS2) may be responsible for development of this form of Turcot syndrome. MLH1 is located on the short arm (p) of chromosome 3 at band number 21.3. PMS2 is located on the short arm (p) of chromosome 7 at band number 22.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 3p21.3” refers to band 21 on the short arm of chromosome 3. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The second type of Turcot syndrome, which is associated with familial adenomatous polyposis, is inherited as an autosomal dominant trait. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
This form of Turcot syndrome results from mutations to the APC gene (for “adenomatous polyposis coli”), which has been mapped to the long arm (q) of chromosome 5 (5q21-q22). Evidence suggests that the APC gene functions as a tumor suppressor gene. Mutations to the APC gene are associated with familial adenomatous polyposis and Gardner syndrome.
Turcot syndrome affects males and females in equal numbers. Approximately 150 cases have been reported in the medical literature.
A diagnosis of Turcot syndrome is made based upon a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests. Because children of an affected parent have a genetic risk of developing Turcot syndrome, regular screening via sigmoidoscopy is required until approximately age 35 to 40 to help ensure early detection and prompt, appropriate treatment. During sigmoidoscopy, a viewing instrument is used to examine the rectum and the last part of the large intestine (sigmoid colon). In addition, in some cases, DNA testing may be available to help detect family members who have inherited certain changes (mutations) of the APC gene or DNA mismatch repair genes, potentially diagnosing the disorder before polyp development. In addition, x-rays of the large intestine may reveal the presence of polyps. X-rays of the brain may reveal the presence of a central nervous system tumor.
Diagnostic testing for Turcot syndrome also includes direct visual examination of the intestines by the insertion of a flexible, tube-like instrument (colonoscope) into the rectum (colonoscopy) or the removal and microscopic examination of small samples of rectal tissue (biopsy).
The treatment of Turcot syndrome is directed toward the specific symptoms that are apparent in each individual. Surgical removal of the large intestine and the rectum (proctocolectomy) may prevent the risk of such malignancies. However, if procedures are performed to remove the large intestine and surgically join the rectum and small intestine (ileoproctostomy), rectal polyps may regress. Therefore, some physicians may recommend such procedures as an alternative to proctocolectomy. In such cases, the remaining rectal region must be regularly examined through sigmoidoscopy to ensure prompt detection and surgical removal or destruction of any new polyps.
In some affected individuals, rapid development of new polyps may necessitate additional surgical treatment, such as removal of the rectum and surgical creation of a connection between the small intestine and the abdominal wall (ileostomy). In other cases, physicians may initially recommend other surgical procedures, such as a technique in which the large intestine is removed (colectomy) and the small intestine and the anus are surgically joined (ileoanal anastomosis).
Affected individuals should also receive periodic neurological screenings to test for the presence of a brain tumor. Treatment for brain tumors depends upon the type, size, and location of the tumor. It may include surgery to remove as much of the tumor as is possible without causing damage to the surrounding tissue. Surgery is often followed or accompanied by radiation and/or chemotherapy treatments.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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