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.
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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].
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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
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