| Gardner's syndrome | |
|---|---|
| Other names | Familial colorectal polyposis, Familial polyposis of the colon |
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| Specialty | Gastroenterology,oncology,medical genetics  |
Gardner's syndrome (also known asGardner syndrome,familial polyposis of the colon,[1] orfamilial colorectal polyposis[2]) is a subtype offamilial adenomatous polyposis (FAP). Gardner syndrome is anautosomaldominant form ofpolyposis characterized by the presence of multiplepolyps in thecolon together with tumors outside the colon.[3] The extracolonic tumors may includeosteomas of the skull,thyroid cancer,epidermoid cysts,fibromas,[4] as well as the occurrence ofdesmoid tumors in approximately 15% of affected individuals.
Desmoid tumors are fibrous tumors that usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. The countless polyps in the colon predispose to the development ofcolon cancer; if the colon is not removed, the chance of colon cancer is considered to be very significant. Polyps may also grow in the stomach,duodenum,spleen,kidneys,liver,mesentery, and small bowel. In a small number of cases, polyps have also appeared in thecerebellum. Cancers related to Gardner syndrome commonly appear in thethyroid, liver and kidneys. The number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon.
The syndrome was first described in 1951.[5] There is no cure at this time, and in its more advanced forms, it is considered a terminal diagnosis with a life expectancy of 35–45 years; treatments are surgery andpalliative care, although somechemotherapy has been tried with limited success.[6]
Gardner syndrome is caused bymutation in theadenomatous polyposis coli (APC gene), located inchromosome5q21 (band q21 on chromosome 5).[3] This gene is also mutant infamilial adenomatous polyposis (FAP), a more common disease that also predisposes to colon cancer. Nuances in the understanding of genetics have caused some disorders to be split into multiple entities, while others merged into one genetic condition. After most of the second half of the 20th century, Gardner syndrome has been merged into FAP and is now considered simply aphenotypic subtype of FAP.[7] FAP is defined by the development of hundreds or thousands of polyps in the colon. Gardner syndrome is set apart as a subtype because, in addition to colonic polyps, there are also extra-colonic growths (both malignant and benign).[8] There are many terms used to describe "APC-associated polyposis condition" including FAP, attenuated FAP, Gardner syndrome, Turcot syndrome, and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). There is a movement toward no longer using the terms Gardner Syndrome or Turcot Syndrome since both are part of the FAP spectrum. Gardner syndrome and Turcot syndrome are regarded primarily for historical interest.[9]
Gardner syndrome is inherited in anautosomal dominant manner.[3] Typically, one parent has Gardner syndrome. Each of their children, male and female alike, are at 50% risk of inheriting the gene for Gardner syndrome.[citation needed]
Gardner syndrome consists of adenomatous polyps of thegastrointestinal tract,Gardner fibromas, desmoid tumors, osteomas, epidermoid cysts, lipomas, dental abnormalities, andperiampullary carcinomas. The incidence of the syndrome is 1:14,025 with an equal sex distribution. It is determined by the autosomal dominant familial polyposis coli gene (APC) onchromosome 5.[5][10]
Gardner syndrome can be identified based on oral findings, including multipleimpacted andsupernumerary teeth, multiple jaw osteomas that give a "cotton-wool" appearance to the jaws, as well as multipleodontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE), in addition to multiple adenomatous polyps of the colon. Gardner syndrome is also associated with familial adenomatous polyposis and may manifest as aggressive fibromatosis (desmoid tumors) of the retroperitoneum.[11]
Desmoid tumors arise most frequently from theaponeurosis of the rectus abdominal muscle of multiparous women. The extra-abdominal form is rare and desmoids of the breast may arise in the mammary gland or may occur as an extension of a lesion arising from the muscles of the chest wall. The incidence of mammary desmoid tumors is less than 0.2% of primary breast neoplasms. In Gardner's syndrome, the incidence ranges from 4% to 17%. Desmoid tumors associated with Gardner's syndrome have been shown to have an alteration of the β-catenin pathway and over express β-catenin.[5]
There is no cure for Gardner Syndrome. Treatments focus on alleviating symptoms and reducing risk of cancer. Treatments for desmoid tumors may include surgery, NSAIDS, anti-estrogen medications, radiation therapy and chemotherapy.[6]
The syndrome is named forEldon J. Gardner (1909–1989), an American geneticist who first described it in 1951.[12]
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