Turcot Syndrome

Turcot Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Turcot Syndrome 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.

Synonyms

  • Brain tumor-polyposis syndrome
  • Glioma-polyposis syndrome

Disorder Subdivisions

  • None

General Discussion

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.

Symptoms

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.

Causes

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.

Affected Populations

Turcot syndrome affects males and females in equal numbers. Approximately 150 cases have been reported in the medical literature.

Standard Therapies

Diagnosis

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).



Treatment

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.

Investigational Therapies

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 web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Yamada T, et al. Textbook of Gastroenterology. 2nd ed. J.B. Lippincott Company; 1995:1944-54.



Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:



Buyse ML. Birth Defects Encyclopedia. Dover, MA; Blackwell Scientific Publications, Inc.; 1990:



JOURNAL ARTICLES

Baeza N, et al., AXIN1 mutations but not deletions in cerebellar medulloblastomas. Oncogene. 2003;22:632-6.



Grips E, et al., Glioblastoma multiforme as a manifestation of Turcot syndrome. Nevenarzt. 2002;73:177-82.



Castillo R, Wilson MM, Turcot syndrome in an elderly adult. J Clin Gastroenterol. 2002;34:449-50.



De Rosa M, et al., Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene. Oncogene. 2003;19:1719:23.



Sunahara M, et al., Turcot syndrome. Nippon Rinsho. 2000;58:1484-9.



Tamiya T, et al., Ganglioglioma in a patient with Turcot syndrome. Case report. J Neurosurg. 2000;92:170-5.



Matsui T, et al., A father and son with Turcot's syndrome: evidence for autosomal dominant inheritance: report of two cases. Dis Colon Rectum. 1998:41:797-801.



Chan TL, et al., Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome. Genes Chromosomes Cancer. 1999;25:75-81.



Suzsui M, et al., Genetic alterations in a patient with Turcot's syndrome. Pathol Int. 1998;48:126-33.



McLaughlin MR, et al., Medulloblastoma and glioblastoma multiforme in a patient with Turcot syndrome. Surg Neurol. 1998;49:295-301.



Mullins KJ, et al., Malignant ependymomas in a patient with Turcot's syndrome: case report and management guidelines. Surg Neurol. 1998;49:290-4.



Fracasso P, et al., Turcot syndrome: case report and nosological aspects. J Exp Clin Cancer Res. 1997;16:433-5.



Paraf F, et al, Brain tumor-polyposis syndrome: two genetic diseases? J Clin Oncol. 1997;15:2744:58.



Hamilton SR, et al., The molecular basis of Turcot syndrome. N Engl J Med. 1995;332:839-47.

Resources

American Brain Tumor Association

8550 W. Bryn Mawr Avenue, Suite 550

Chicago, IL 60631

USA

Tel: (773)577-8750

Fax: (773)577-8738

Tel: (800)886-2282

Email: info@abta.org

Internet: http://www.abta.org



March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



Familial GI Cancer Registry

Mt. Sinai Hospital

Joseph and Wolf Lebovic Health Complex

600 University Avenue

Toronto

Ontario, M5T 3L9

Canada

Tel: 4165964200

Fax: 4165855024

Email: tberk@mtsinai.on.ca

Internet: http://www.mountsinai.on.ca/care/fgicr



Johns Hopkins Hereditary Colorectal Cancer Registry

Johns Hopkins Hospital

1830 East Monument Stree

Room 431

Baltimore, MD 21205

Tel: (410)955-2635

Fax: (410)614-8337

Tel: (888)772-6566

Email: hccregistry@jhmi.edu

Internet: http://www.hopkins-gi.org



American Cancer Society, Inc.

250 Williams NW St

Ste 6000

Atlanta, GA 30303

USA

Tel: (404)320-3333

Tel: (800)227-2345

TDD: (866)228-4327

Internet: http://www.cancer.org



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



National Cancer Institute

6116 Executive Blvd Suite 300

Bethesda, MD 20892-8322

USA

Tel: (301)435-3848

Tel: (800)422-6237

TDD: (800)332-8615

Email: cancergovstaff@mail.nih.gov

Internet: http://www.cancer.gov



Southeastern Hereditary Colorectal Cancer Registry

University Hospital

1350 Walton Way

Augusta, GA 30910-3599

USA

Tel: (706)774-8900

Fax: (706)774-8915

Email: cwheeler@uh.org



Brain Tumour Foundation of Canada

620 Colborne Street

Suite 301

London

Ontario, N6B 3R9

Canada

Tel: 5196427755

Fax: 5196427192

Tel: 8002655106

Email: braintumour@braintumour.ca

Internet: http://www.braintumour.ca



Brain Tumour UK

Tower House

Latimer Park

Chesham

Bucks, HP5 1TU

United Kingdom

Tel: 08454500386

Email: enquiries@braintumouruk.org.uk

Internet: http://www.braintumouruk.org.uk



Children's Brain Tumor Foundation

274 Madison Avenue, Suite 1004

New York, NY 10016

United States

Tel: (212)448-1595

Fax: (212)448-1022

Tel: (866)228-4673

Email: info@cbtf.org

Internet: http://www.cbtf.org



OncoLink: The University of Pennsylvania Cancer Center Resource

3400 Spruce Street

2 Donner

Philadelphia, PA 19104-4283

USA

Tel: (215)349-8895

Fax: (215)349-5445

Email: hampshire@uphs.upenn.edu

Internet: http://www.oncolink.upenn.edu



Brain Tumor Foundation for Children, Inc.

6065 Roswell Road Suite 505

Atlanta, GA 30328-4015

USA

Tel: (404)252-4107

Fax: (404)252-4108

Email: info@braintumorkids.org

Internet: http://www.braintumorkids.org



Rare Cancer Alliance

1649 North Pacana Way

Green Valley, AZ 85614

USA

Internet: http://www.rare-cancer.org



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

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Pediatric Brain Tumor Foundation

302 Ridgefield Court

Asheville, NC 28806

Tel: (828)665-6891

Fax: (828)665-6894

Tel: (800)253-6530

Email: pbtfus@pbtfus.org

Internet: http://www.pbtfus.org



Friends of Cancer Research

1800 M Street NW

Suite 1050 South

Washington, DC 22202

Tel: (202)944-6700

Email: info@focr.org

Internet: http://www.focr.org



Cancer.Net

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

Email: contactus@cancer.net

Internet: http://www.cancer.net/



National Brain Tumor Society

124 Watertown Street, Suite 2D

Watertown, MA 02472

Tel: (617)924-9997

Fax: (617)924-9998

Tel: (800) 770-8287

Email: info@braintumor.org

Internet: http://www.braintumor.org



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 myCigna.com. 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 http://www.rarediseases.org/search/rdblist.html.

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