Familial adenomatous polyposis

CHRPE - Congenital hypertrophy of the retinal pigment epithelium

Familial Adenomatous Polyposis (FAP)

Familial Adenomatous Polyposis (FAP) is an autosomal dominant inherited condition characterized by the formation of numerous adenomatous polyps mainly in the epithelium of the large intestine. Although these polyps are initially benign, they can transform into colon cancer if not treated. FAP exists in three known variants: FAP and attenuated FAP are caused by defects in the APC gene on chromosome 5, while autosomal recessive FAP, or MYH-associated polyposis, results from mutations in the MUTYH gene on chromosome 1. FAP is the most severe and common form. Early detection and removal of the polyps can significantly reduce the risk of cancer spreading beyond the colon.

Micrograph of a tubular adenoma, the colorectal cancer precursor most commonly associated with FAP

Colectomy specimen showing numerous polyps throughout the large bowel

Root Cause

The genetic mutation in FAP affects tumor suppressor genes, diminishing the body's defense against aged cells turning cancerous. This alteration allows cells of the intestinal wall to evolve into cancerous polyps over time. Attenuated familial adenomatous polyposis, a less severe form, results from a partially functional APC gene, leading to fewer polyps and a later onset of cancer, typically between 40 and 70 years old. The autosomal recessive variant necessitates both parents to be carriers.

Symptoms and Diagnosis

Patients develop hundreds to thousands of polyps in the colon and sometimes other areas, which may bleed or lead to anemia. Advanced cases can lead to weight loss, altered bowel habits, or metastasis. Diagnosis is confirmed through colonoscopy, genetic testing, or observing clinical presentation. It's crucial for at-risk individuals to undergo regular intestinal tract monitoring from puberty or early adulthood.

Genetics

FAP's genetics involve mutations in the APC gene or the MUTYH gene, leading to a lack of proper tumor suppression. The APC gene plays a key role in cell communication and growth regulation, while the MUTYH gene is involved in DNA repair. Mutations in these genes disrupt normal cellular functions, increasing cancer risk.

Management

Management of FAP includes identifying at-risk individuals through family history or genetic testing, regular monitoring of the intestinal tract, and surgical intervention when necessary. Prophylactic surgery, such as colectomy, is often recommended to prevent colon cancer. Medications, like NSAIDs, may slow polyp malignancy, but surgery is a primary treatment to remove the affected colon sections.

Prognosis

Early detection and treatment of FAP significantly improve outcomes. If polyps are confined to the colon's inner wall, surgical removal can prevent cancer spread. Post-surgery, regular monitoring is essential to detect any new polyps in the remaining colon sections.

Epidemiology

FAP affects 1 in 10,000 to 1 in 15,000 births. Without treatment, colon cancer is almost inevitable by middle age. The attenuated form of FAP presents fewer polyps and a later onset of cancer, providing different management options.

Polyposis registries

Because of the genetic nature of FAP, polyposis registries have been developed around the world. The purpose of these registries is to increase knowledge about the transmissibility of FAP, but also to document, track, and notify family members of affected individuals.

Glossary

• Adenomatous polyps - Benign growths that may develop into cancer if not removed.
• Autosomal dominant - A pattern of inheritance where a mutation in just one of the two gene copies is sufficient to cause a disorder.
• Chromosome 5 - One of the 23 pairs of human chromosomes, home to the APC gene associated with FAP.
• Chromosome 1 - One of the 23 pairs of human chromosomes, where the MUTYH gene associated with autosomal recessive FAP is located.
• Colonoscopy - A diagnostic procedure to examine the interior of the colon for polyps and cancer.
• Genetic testing - Testing conducted to identify genetic mutations associated with diseases like FAP.

See also

• Colorectal cancer
• Polyp (medicine)
• Adenoma
• Adenomatous polyps
• Colorectal polyp
• Genetic testing

External links

Classification	ICD-10: C18 , D12 OMIM: 175100 MeSH: D011125 DiseasesDB: 4678
External resources	eMedicine: med/769 Orphanet: 733

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