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Gardner syndrome

Randall W Burt, MD
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Shilpa Grover, MD, MPH


Gardner, in the early 1950s, described a kindred with intestinal characteristics of familial adenomatous polyposis (FAP), but also with a number of extracolonic growths, including osteomas, epidermal cysts and fibromas [1]. Dental abnormalities, desmoid tumors and other lesions were later recognized as additional manifestations of the underlying genetic defect [2,3]. The constellation of inherited colonic adenomatosis together with these extracolonic lesions has become known as Gardner syndrome (GS).

This topic review will discuss each of the extraintestinal manifestations of FAP that historically have defined GS. Gastric, duodenal, and colonic polyp and cancer issues are discussed in a separate section on FAP. Genetic testing is now also available for FAP and GS since both arise from mutations of the same gene [4]. It should be noted that GS is now considered a subcategory of FAP, characterized by the extraintestinal manifestations to be reviewed below that occur in addition to the intestinal polyposis of FAP. Issues related to genetic testing are also presented in the section on FAP. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis" and "Familial adenomatous polyposis: Screening and management of patients and families".)


Shortly after discovery of the adenomatous polyposis coli (APC) gene, the gene responsible for familial adenomatous polyposis (FAP), it became apparent that both FAP and Gardner syndrome (GS) arose from APC mutations [2,3]. FAP is characterized by hundreds to thousands of colonic adenomatous polyps that most often emerge in the second and third decades of life. Colon cancer is inevitable if the colon is not removed. Polyposis is also usually observed in the stomach, duodenum, and small bowel, although the cancer risk in these locations is far less than in the colon. Inheritance is autosomal dominant with near complete penetrance of the gastrointestinal phenotype but with variable penetrance of the extraintestinal manifestations of the disease.

GS cannot be separated from FAP when considering studies that describe its overall prevalence. Estimates for the prevalence of the combined syndromes vary from 1 in 6850 to 1 in 31,250 people (2.29 to 3.2 cases per 100,000 persons) [5-7]. Prevalence appears fairly constant throughout the world with men and women affected equally. Twenty to 30 percent of newly diagnosed cases, ie, those not belonging to previously identified families, appear to represent new mutations [5]. New cases may also arise from mosaic inheritance, which implies that a mutation occurred in parent's sperm or egg cells, but not in other cells of the body, so the parent did not have clinical disease [8].

It was once believed that GS patients exhibited fewer and more distinct colonic polyps. However, continued study has demonstrated that the gastrointestinal polyp and cancer phenotypes, although variable, are identical for both GS and FAP. Colonic polyp number depends to some degree on where the mutation occurs in the APC gene [9]. Mutations in the center of the gene (often called the mutation cluster region) give rise to dense polyposis, with 5000 or more colonic polyps [10] when the disease is fully developed. If mutations occur proximal or distal to this central gene location, colonic polyps average approximately 1000 with full expression. Mutations in the extreme proximal or distal locations of the APC gene, or in certain areas of exon none, are associated with many fewer polyps (often less than 100). This clinical variation is referred to as attenuated FAP. Extraintestinal growths do not correlate with polyp density but have some correlation with mutation location [2,10,11].


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Literature review current through: Sep 2016. | This topic last updated: Jan 6, 2015.
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