Pediatric Gardner Syndrome

Updated: Aug 06, 2015
  • Author: Michael Gilger, MD; Chief Editor: Carmen Cuffari, MD  more...
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Overview

Background

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.

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Pathophysiology

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.

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Etiology

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

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Epidemiology

United States statistics

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.

International statistics

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]

Racial differences in incidence

Gardner syndrome has no racial predilection.

Sexual differences in incidence

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

Age-related differences in incidence

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.

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Prognosis

Complications

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.

Mortality/morbidity

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]

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Patient Education

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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