Gardner Syndrome

Article Author:
Ahmad Charifa
Article Editor:
Xuchen Zhang
10/27/2018 12:31:36 PM
PubMed Link:
Gardner Syndrome


Gardner syndrome is a phenotypic variant of familial adenomatous polyposis. It is an autosomal dominant disease characterized by numerous adenomatous polyps lining the intestinal mucosal surface with a high potential for malignancy. Gardner first described the syndrome in 1951. He described the presence of multiple polyps in the colon together with tumors outside the colon. The extracolonic manifestations may include intestinal polyposis, desmoids, osteomas, and epidermoid cysts. Typically, patients with Gardner syndrome may present with osteomas of the mandible and skull, epidermal cysts, or fibromatosis. These manifestations are often found to be asymptomatic but may present with pruritus, inflammation, and rupture. Various non-cutaneous manifestations also exist with this syndrome. A characteristic finding is bilateral, multiple, pigmented, ocular fundus lesions, known as congenital hypertrophy of the retinal epithelium. The development of intestinal polyposis and colorectal adenocarcinoma are key features of Gardner syndrome. Other neoplasms have also been found, such as duodenal carcinomas around the ampulla of Vater, hepatoblastoma, adrenal adenomas, papillary or follicular thyroid cancer.


A genetic connection to the development of Gardner syndrome has been shown within band 5q21, which is associated with the adenomatous polyposis coli (APC) gene, located on chromosome 5, a tumor suppressor gene responsible for producing the APC protein that regulates cell growth via appropriate timing in the cell cycle. Gardner syndrome patients suffer from an aberration of this gene which leads to uncontrolled cell growth. In addition to such genetic mutations, a loss of DNA methylation, a mutation of the RAS gene on chromosome 12, a deletion of the colon cancer gene (DCC) on chromosome 18, as well as, a mutation in TP53 gene located on chromosome 17 have also been linked as a possible cause of Gardner syndrome.


The prevalence of Gardner syndrome is 1 per one million people within the United States, with an incidence of 1 in 8000 individuals.  Most commonly, Gardner syndrome patients present with epidermoid cysts.


The APC gene, located on the long arm of chromosome 5, is a tumor suppressor gene, which is responsible for the production of a protein that plays a significant role in cell division, regulation, and growth. It is specifically involved in controlling how often a cell divides and the manner of attachment of the cell to other cells within the tissue and the cell polarization and the morphology of some of its structures. It also serves as a determinant of the cell’s mobility and direction in terms of chromosomal movement during cell division. Specifically, the protein beta-catenin, controlled by the APC gene, prevents those proteins responsible for stimulating cell division from being overly activated, thereby, preventing cell overgrowth and proliferation. Frequently it is the inactivation of the APC gene and the subsequent, inactivation of beta-catenin that is observed in cancerous cells.

History and Physical

The following are symptoms commonly associated with Gardner syndrome: patients may be asymptomatic or self-report cramping, diarrhea, rectal bleeding, constipation secondary to the obstruction, and/or vomiting. In addition, multiple gastrointestinal polyps (typically presenting in the colon) may be observed, developing extra teeth, cysts may develop under the skin, bony tumors on bones, such as the skull, as well as, fibromas. The risk of developing colon cancer is also much greater in a Gardner syndrome patient.


The disorder can be diagnosed via a medical examination and discussion of medical and familial history, self-reported symptoms, endoscopy of the lower gastrointestinal (GI) tract, and, through the use of molecular testing of the blood for screening of genetic mutations known to be linked to the disease. Pre-natal genetic testing can also be performed, and if positive, endoscopic screenings for polyps can begin as early as 10 years of age.

Treatment / Management

Prevention is the most common approach to treatment for those individuals who are aware of the respective familial inheritance or once this is discovered. This type of treatment protocol can include a healthy diet, the use of NSAIDs such as sulindac, or a COX2 inhibitor like celecoxib which can aid in the stifling of the growth of polyps in the colon, especially since it is well known that Gardner syndrome patients are at a greater risk for developing colon cancer. Surveillance via lower GI endoscopies is also recommended to monitor polyp growth and development and to ascertain their transformation into malignant tumors. If more than 20 or more polyps are present, removal of the colon is recommended to reduce the risk for colon cancer development.

Differential Diagnosis

Gardner syndrome, FAP, Turcot syndrome, and attenuated forms of familial polyposis are the main phenotypes that are associated with APC gene mutation. Molecular studies show that these four types have an associated mutation on chromosome 5q21. However, unlike the other phenotypes, Gardner syndrome is characterized by polyps in the colon, osteomas, and abnormalities in the retinal epithelium. Both Gardner syndrome and Turcot syndrome may present with skin manifestations, but the former presents more so with epi-dermoid cysts and the latter with cafe-au-lait spots.

Surgical Oncology

If 20 or more polyps are present, then it is recommended that the colon be removed to reduce the risk of colon cancer development.

Radiation Oncology

Radiation does not seem to be an appropriate form of treatment due to its ineffectiveness.


There appears to be no official staging that is clinically significant, as is common with other types of cancers, other than to consider the number of polyps present, the degree of symptoms, and the transformation of benign tumors into malignant cells.


There is no cure for Gardner syndrome. The prognosis for a person diagnosed with Gardner syndrome varies; however, a patient with an APC gene mutation is almost certain to develop colon cancer by approximately the age of 40 if surgery is not performed and polyp growth controlled. Surveillance and management of symptoms are the most effective treatment options. Annual physical examinations, thyroid function evaluations beginning in the late teenage years, screenings 2 the colon can start as early as the age of 10 (continue every 1 to two years), and, possibly treatment with NSAIDs such as sulindac and COX2 inhibitors are all options to bettering the overall prognosis of a patient suffering from Gardner syndrome.

Pearls and Other Issues

Early detection of Gardner syndrome is crucial due to the high probability that it will transmute to malignancy over time. The disease is genetically based and follows an autosomal dominant inheritance pattern. It typically presents as gastrointestinal polyps, skin, and soft tissue tumors, as well as, multiple osteomas. The cutaneous based presentations often include but are not limited to epidermoid cysts, desmoid, and other benign tumors. The progression from an adenoma to carcinoma includes a cellular cascade of events at the tyrosine kinase level of the cell cycle. The disorder is considered a variant of familial adenomatous polyposis, although it manifests in areas other than the colon.


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