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Familial adenomatous polyposis

What is familial adenomatous polyposis?

Familial adenomatous polyposis, often called FAP, is an inherited colorectal cancer syndrome. This cancer usually develops in the lower part of the digestive system, including the large intestine (colon) and rectum. People with the classic type of familial adenomatous polyposis may begin to develop multiple noncancerous (benign) polyps (growths) in the colon as early as their teenage years. The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is about 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis, in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is about 55 years.

In people with classic familial adenomatous polyposis, the number of polyps increases with age and can include hundreds to thousands of polyps. Unless the colon is removed, these polyps will become malignant (cancerous). Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be initiated by abdominal surgery. With classic familial adenomatous polyposis and its attenuated variant, other benign and malignant tumors are sometimes found in other places in the body, especially the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. People who have many of these other growths in addition to colon polyps are sometimes referred to as having Gardner syndrome.

A milder type of familial adenomatous polyposis, called autosomal recessive familial adenomatous polyposis, has also been identified. People with the autosomal recessive type of this disorder have fewer polyps than those with the classic type, typically fewer than 100, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than the classic and attenuated types of familial adenomatous polyposis.

How common is familial adenomatous polyposis?

Familial adenomatous polyposis affects about 1 in 30,000 people, with 800 to 1,000 new cases detected each year.

What genes are related to familial adenomatous polyposis?

Mutations in the APC and MUTYH genes cause familial adenomatous polyposis.

Mutations in the APC gene cause both classic and attenuated familial adenomatous polyposis. Mutations in the APC gene affect the ability of the cell to maintain normal growth and function. Cell overgrowth resulting from mutations in the APC gene leads to the colon polyps seen in familial adenomatous polyposis. Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.

Mutations in the MUTYH gene cause autosomal recessive familial adenomatous polyposis (also called MYH-associated polyposis). Mutations in the MUTYH gene prevent cells from correcting mistakes that are made when DNA is copied in preparation for cell division (DNA replication). As these mistakes build up in a person's DNA, the likelihood of cell overgrowth increases, leading to colon polyps and the possibility of colon cancer.

How do people inherit familial adenomatous polyposis?

Familial adenomatous polyposis can have different inheritance patterns and different genetic causes.

When familial adenomatous polyposis results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

When familial adenomatous polyposis results from mutations in the MUTYH gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Familial Adenomatous Polyposis on Wikipedia

'''Familial adenomatous polyposis''' ('''FAP''') is an inherited condition in which numerous polyps to form in the epithelium of the colon (anatomy). While these are benign, they may become malignant, predisposing patients to colorectal cancer.

Signs and symptoms

From the age of 16 onward, patients develop hundreds to thousands of polyps. These may bleed, leading to admixture of blood in the stool. If the blood is not visible, it is still possible for the patient to develop anemia due to gradually developing iron deficiency. If malignancy develops (the median age in FAP patients is about 40), this may present with weight loss, altered bowel habit, or even with metastasis in the liver or elsewhere. The genetic determinant in familial polyposis may also predispose carriers to other malignancies, e.g. of the duodenum and stomach. Other signs that may point at FAP are pigmented lesions of the retina ("congenital hypertrophy of the retinal pigment"), jaw cysts, sebaceous cysts, and osteomata (benign bone tumors). The combination of polyposis, osteomas, fibromas and sebaceous cysts is termed ''Gardner syndrome'' (with or without abnormal scarring).

Diagnosis and treatment

In patients with a strong family of colorectal cancer and symptoms suggestive of polyposis, colonoscopy is indicated, with biopsy of a number of polyps (especially of those that appear dysplasia). Blood tests (liver enzymes) and medical ultrasonography of the abdomen are often performed to rule out metastasis to the liver. Genetic testing provides the ultimate diagnosis in 95%; genetic counseling is usually needed in families where FAP has been diagnosed. Testing may also aid in the diagnosis of borderline cases in families that are otherwise known to have the FAP mutation.

Pathophysiology

FAP is due to mutations in the ''APC'' gene, which is located ...   [ Read More ]


External Resources

Fap.org: Familial Adenomatous Polyposis - Aimed for those with hereditary colon cancer. Provides information, FAQs, links and a message board.

SandDude on Gardner's Syndrome - Patient's point of view on this condition (familial adenomatous polyposis), experiences with the condition and after colostomy, information, and related links.

Familial Gastrointestinal Cancer Registry - A family study centre at Mount Sinai Hospital, Toronto, for rare inherited colorectal cancer syndromes, including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), Peutz-Jeghers syndrome, juvenile polyposis, and other polyposis syndromes.


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Familial Mediterranean fever
Familial atrial fibrillation
Familial lipoprotein lipase deficiency
Familial encephalopathy with neuroserpin inclusion bodies

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