Gardner's syndrome (also known as Gardner syndrome, familial polyposis of the colon, or familial colorectal polyposis) is a subtype of

familial adenomatous polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into c ...

(FAP). Gardner syndrome is an autosomal dominant form of polyposis characterized by the presence of multiple polyps in the colon together with tumors outside the colon. The extracolonic tumors may include

osteoma An osteoma (plural: "osteomata") is a new piece of bone usually growing on another piece of bone, typically the skull. It is a benign tumor. When the bone tumor grows on other bone it is known as "homoplastic osteoma"; when it grows on other tiss ...

s of the skull,

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

, epidermoid cysts, fibromas, as well as the occurrence of desmoid 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 of

colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...

; 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 The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine ...

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

, mesentery, and small bowel. In a small number of cases, polyps have also appeared in the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cere ...

. Cancers related to Gardner syndrome commonly appear in the

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The t ...

, 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. 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 and

palliative care Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wi ...

, although some

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

has been tried with limited success.

Cause

Gardner syndrome is caused by

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

in the adenomatous polyposis coli (APC gene), located in

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...

5q21 (band q21 on chromosome 5). This gene is also mutant in

(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 a phenotypic subtype of FAP. 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). 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.

Genetics

Gardner syndrome is inherited in an autosomal dominant manner. 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.

Diagnosis

Gardner syndrome consists of adenomatous polyps of the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...

, Gardner fibromas, desmoid tumors, osteomas, epidermoid cysts, lipomas, dental abnormalities, and periampullary 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) on chromosome 5. Gardner syndrome can be identified based on oral findings, including multiple impacted and supernumerary teeth, multiple jaw osteomas that give a "cotton-wool" appearance to the jaws, as well as multiple odontomas, 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.DeVita. ''Cancer, Principles and Practice of Oncology'', 8th Ed. p. 1742. Desmoid tumors arise most frequently from the aponeurosis 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.

Treatment

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.

Eponym

The syndrome is named for

Eldon J. Gardner Eldon may refer to: Places Australia * Eldon Range, Tasmania, a mountain range Canada * Eldon, Alberta, a locality * Eldon Parish, New Brunswick * Eldon Township, Ontario, a former municipality * Eldon, Ontario, a former railway stop * Eldon, P ...

(1909–1989), a geneticist who first described it in 1951.

References

External links

* {{Cytoskeletal defects Gastrointestinal cancer Autosomal dominant disorders Hereditary cancers Genodermatoses Congenital oral disorders Syndromes with tumors Syndromes affecting the gastrointestinal tract