Pediatric Gardner Syndrome

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Pediatric Gardner Syndrome

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Gardner syndrome is a familial polyposis syndrome, better classified as a variant of familial adenomatous polyposis (FAP). In Gardner syndrome, the symptoms of classic FAP syndrome are present; this consists of the development of approximately 500-2500 colonic adenomas that blanket the surface of the colonic mucosa. Multiple adenomas are also often present throughout the GI tract, especially in the periampullary region and the stomach. [1]

In addition to the classic findings of FAP, other findings include multiple osteomas (commonly of the skull, mandible, and long bones), dental abnormalities (including supernumerary teeth and odontomas), epidermal cysts, thyroid carcinoma, pancreatic adenocarcinoma, congenital hypertrophy of the retinal pigmented epithelium (CHRPE), and fibromatosis or desmoid tumors (commonly in the abdominal wall and retroperitoneum). [2, 3, 4] Less commonly, lipomas, leiomyomas, neurofibromas, hepatoblastomas, and pigmented skin lesions are also seen.

The pathogenesis of both FAP and Gardner syndrome is caused by mutations on the adenomatous polyposis coli (APC) gene on chromosome 5q21. [5, 6] The loss or mutation of this gene is thought to lead to the formation of colonic adenomas and fulfills the first hit of the double hit concept of colorectal cancer development. [7] The loss of APC function prevents apoptosis and allows beta-catenin to build up within cells, which subsequently stimulates cell growth resulting in development of adenomas. [8]

What is exceptional in patients with FAP and Gardner syndrome is the development of hundreds to thousands of these adenomas. This puts them at increased risk, simply by numbers alone, of ultimately having one or more adenomas undergo malignant transformation into adenocarcinoma or colorectal cancer.

Gardner syndrome is a variant of FAP, which is caused by a germline mutation of the APC tumor suppressor gene on chromosome 5q21.

The estimated frequency of FAP in the general population in the United States ranges from 1 in 8,000 to 1 in 14,000. [9] No specific estimate is available for Gardner syndrome.

The estimated frequency of FAP in the general population in the world is the same as the United States, ranging from 1 in 8,000 to 1 in 14,000. [9]

Gardner syndrome has no racial predilection.

The male-to-female ratio in patients with Gardner syndrome is 1:1. [9]

Patients with a positive family history of FAP, who carry the FAP mutation, should have their screening colonoscopy performed at 12 years of age. If multiple adenomas are identified on colonoscopy, patients should be considered for colectomy.

Complications of Gardner syndrome have been mentioned previously and include colorectal adenocarcinoma, invasive fibromatosis, thyroid carcinoma, and duodenal and periampullary adenocarcinoma. In patients who have a retained rectal pouch after surgery, rectal adenocarcinoma may be a complication.

The main cause of morbidity and mortality in patients with Gardner syndrome stems from the high frequency of colorectal adenocarcinoma in these patients, which is essentially 100% unless the patients are treated.

In patients who have had a prophylactic colectomy, a common cause of morbidity and mortality is periampullary adenoma and adenocarcinoma. [10]

Desmoid tumors may be a significant cause of morbidity, affecting 10-25% percent of patients. [11] Although these tumors are considered to be benign because they do not metastasize, they can show an infiltrative pattern of local growth. This growth can extend along fascial planes and may cause compression of blood vessels and nerves as well as other abdominal organs including the small bowel, colon, bladder, and ureter. [12]

Pancreatic adenocarcinoma carries a significant morbidity and mortality risk as well. In patients treated by surgical resection, the 1-year survival rate is approximately 25%, and the overall 5-year survival rate is 6%. [13]

Lifelong compliance with screening for tumors is essential in patients with FAP and Gardner syndrome. Patients must be well educated by physicians in the importance of screening. [14] Family members of affected individuals must also be well informed that they are at risk for Gardner syndrome.

Haggitt RC, Reid BJ. Hereditary gastrointestinal polyposis syndromes. Am J Surg Pathol. 1986 Dec. 10(12):871-87. [Medline].

Wehrli BM, Weiss SW, Yandow S, Coffin CM. Gardner-associated fibromas (GAF) in young patients: a distinct fibrous lesion that identifies unsuspected Gardner syndrome and risk for fibromatosis. Am J Surg Pathol. 2001 May. 25(5):645-51. [Medline].

Lynch HT, Thorson AG, McComb RD, Franklin BA, Tinley ST, Lynch JF. Familial adenomatous polyposis and extracolonic cancer. Dig Dis Sci. 2001 Nov. 46(11):2325-32. [Medline].

Giardiello FM, Offerhaus GJ, Lee DH, Krush AJ, Tersmette AC, Booker SV. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993 Oct. 34(10):1394-6. [Medline].

Bienz M. APC. Curr Biol. 2003 Mar 18. 13(6):215-6. [Medline].

Turina M, Pavlik CM, Heinimann K, Behrensmeier F, Simmen HP. Recurrent desmoids determine outcome in patients with Gardner syndrome: a cohort study of three generations of an APC mutation-positive family across 30 years. Int J Colorectal Dis. 2013 Jun. 28(6):865-72. [Medline].

Knudson AG. Two genetic hits (more or less) to cancer. Nat Rev Cancer. 2001 Nov. 1(2):157-62. [Medline].

Huss S, Nehles J, Binot E, Wardelmann E, Mittler J, Kleine MA, et al. ß-catenin (CTNNB1) mutations and clinicopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013 Jan. 62(2):294-304. [Medline].

Giardiello FM, Brensinger JD, Petersen GM. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology. 2001 Jul. 121(1):198-213. [Medline].

Offerhaus GJ, Giardiello FM, Krush AJ, Booker SV, Tersmette AC, Kelley NC, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology. 1992 Jun. 102(6):1980-2. [Medline].

Sturt NJ, Clark SK. Current ideas in desmoid tumours. Fam Cancer. 2006. 5(3):275-85; discussion 287-8. [Medline].

Heiskanen I, Järvinen HJ. Occurrence of desmoid tumours in familial adenomatous polyposis and results of treatment. Int J Colorectal Dis. 1996. 11(4):157-62. [Medline].

Cancer Facts & Figures 2010. American Cancer Society. Available at http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-026238.pdf. Accessed: Jan 2, 2011.

Douma KF, Bleiker EM, Aaronson NK, Cats A, Gerritsma MA, Gundy CM. Long-term compliance with endoscopic surveillance advice for familial adenomatous polyposis (FAP). Colorectal Dis. 2009 Jul 10. [Medline].

Iaquinto G, Fornasarig M, Quaia M, Giardullo N, D’Onofrio V, Iaquinto S, et al. Capsule endoscopy is useful and safe for small-bowel surveillance in familial adenomatous polyposis. Gastrointest Endosc. 2008 Jan. 67(1):61-7. [Medline].

Johnson MD, Mackey R, Brown N, Church J, Burke C, Walsh RM. Outcome based on management for duodenal adenomas: sporadic versus familial disease. J Gastrointest Surg. 2010 Feb. 14(2):229-35. [Medline].

Loccufier A, Vanhulle A, Moreels R, Deruyter L, Legley W. Gardner syndrome and desmoid tumors. Acta Chir Belg. 1993 Sep-Oct. 93(5):230-2. [Medline].

Jones IT, Jagelman DG, Fazio VW, Lavery IC, Weakley FL, McGannon E. Desmoid tumors in familial polyposis coli. Ann Surg. 1986 Jul. 204(1):94-7. [Medline]. [Full Text].

Half E, Arber N. Colon cancer: preventive agents and the present status of chemoprevention. Expert Opin Pharmacother. 2009 Feb. 10(2):211-9. [Medline].

Lynch PM, Ayers GD, Hawk E, Richmond E, Eagle C, Woloj M. The safety and efficacy of celecoxib in children with familial adenomatous polyposis. Am J Gastroenterol. 2010 Jun. 105(6):1437-43. [Medline].

Vasen HF, Möslein G, Alonso A, Aretz S, Bernstein I, Bertario L, et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008 May. 57(5):704-13. [Medline].

Michael Gilger, MD Gastrointestinal Pathologist, Colorado GI Pathology, Centennial Pathologists

Michael Gilger, MD is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Mark A Gilger, MD Professor of Pediatrics, Chief of Pediatric Gastroenterology, Hepatology and Nutrition, Director of Clinical Fellowship Training in Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine; Chief, Gastroenterology and Nutrition Service, Texas Children’s Hospital

Mark A Gilger, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Gastrointestinal Endoscopy, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Crohn’s and Colitis Foundation of America

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers’ bureau.

Jorge H Vargas, MD Professor of Pediatrics and Clinical Professor of Pediatric Gastroenterology, University of California, Los Angeles, David Geffen School of Medicine; Consulting Physician, Department of Pediatrics, University of California at Los Angeles Health System

Jorge H Vargas, MD is a member of the following medical societies: American Liver Foundation, Latin American Society of Pediatric Gastroenterology, Hepatology & Nutrition, American Society for Gastrointestinal Endoscopy, American Society for Parenteral and Enteral Nutrition, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Pediatric Gardner Syndrome

Research & References of Pediatric Gardner Syndrome|A&C Accounting And Tax Services
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Pediatric Gardner Syndrome

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