familial adenomatous polyposis 1

Familial Adenomatous Polyposis (FAP): A Rare Inherited Condition

Familial adenomatous polyposis (FAP) is a rare, inherited condition caused by a defect in the adenomatous polyposis coli (APC) gene [2]. This genetic disorder predisposes individuals to developing colon cancer, with a lifetime risk of nearly 100% [3].

Characteristics of FAP

• FAP leads to the growth of hundreds to thousands of non-cancerous (benign) polyps in the colon and rectum [8].
• These polyps are usually small growths that appear on the inner walls of the colon and rectum, often starting to develop during the second decade of life [7].
• FAP is characterized by the development of hundreds to thousands of adenomas in the rectum and colon during the second decade of life [7].

Causes and Risk Factors

• FAP is an inherited condition caused by a defect in the APC gene, which increases the risk of developing colon cancer.
• Individuals with a family history of FAP are at higher risk of inheriting the condition.

Symptoms and Diagnosis

• The symptoms of FAP may not be apparent until hundreds to thousands of polyps have formed in the colon and rectum.
• A diagnosis of FAP is typically made through genetic testing, which can identify the APC gene mutation responsible for the condition.

References: [1] - Not provided (user's query) [2] - Jun 30, 2021 [3] - Familial adenomatous polyposis (FAP) is a hereditary syndrome that predisposes you to developing colon cancer. The lifetime risk is near 100%. [7] - Familial adenomatous polyposis (FAP) is characterized by the development of hundreds to thousands of adenomas in the rectum and colon during the second decade ... [8] - Familial adenomatous polyposis (FAP) leads to the growth of hundreds to thousands of non-cancerous (benign) polyps in the colon and rectum.

Signs and Symptoms of Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is a rare, inherited condition characterized by the growth of hundreds or even thousands of polyps in the colon and rectum. The main sign of FAP is the presence of these polyps, which can start to appear as early as the teenage years.

Common Symptoms:

• Hundreds or thousands of polyps growing in the colon and rectum
• Dental abnormalities (e.g., jaw tumors)
• Tumors of the connective tissue (desmoid tumors)
• Benign and malignant tumors of the duodenum, liver, bones, skin, and other tissues

Early Detection is Critical:

If left untreated, nearly all cases of FAP progress to colorectal cancer. Therefore, early detection and management are crucial in preventing this progression.

References:

• [1] The presence of hundreds or thousands of polyps growing in the colon and rectum is a common symptom of FAP (Source: #2).
• [2] Dental abnormalities can be a sign of FAP (Source: #3).
• [3] Tumors of the connective tissue, such as desmoid tumors, are associated with FAP (Source: #3).
• [4] If left untreated, nearly all cases of FAP progress to colorectal cancer (Source: #12).

Diagnostic Tests for Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is a rare, inherited disorder characterized by the development of numerous polyps in the colon and rectum. Early diagnosis and treatment are crucial to prevent colorectal cancer. Here are some diagnostic tests used to detect FAP:

• Genetic Testing: Molecular genetic testing is now the primary method for establishing a diagnosis of FAP. This test detects germline pathogenic variants in the APC gene, which is responsible for the condition [10][11].
• Sigmoidoscopy and Colonoscopy: These procedures involve inserting a flexible tube with a camera into the rectum to inspect the colon and rectum for polyps. They are recommended annually starting at age 10-12 years for individuals at risk of FAP, including those with a family history or genetic diagnosis [1][8].
• Complete Blood Cell (CBC) Count: A CBC is used to monitor the effects of treatment and detect any potential complications.
• Alpha-fetoprotein (AFP) Blood Test: This test is performed in children with FAP until age 5 years as part of a comprehensive evaluation.

Screening Tests for Individuals at Risk

For individuals who have an APC gene variant or a first-degree relative with FAP, screening tests may be recommended. These include:

• Annual Sigmoidoscopy or Colonoscopy: Starting at age 10-12 years
• Genetic Testing: To confirm the presence of an APC gene variant

Early Detection and Treatment

Early detection and treatment are critical in preventing colorectal cancer in individuals with FAP. Regular screening tests, followed by surgery if necessary, can significantly improve outcomes.

References:

[1] American College of Gastroenterology. (n.d.). Familial Adenomatous Polyposis (FAP). Retrieved from https://gi.org/clinical-practice-guidelines/familial-adenomatous-polyposis-fap/

[10] Aihara, H., et al. (2014). The diagnosis of FAP relies primarily on clinical findings on the number and history of colorectal adenomatous polyps. Individuals with 100 or more polyps... [5]

[11] Familial Adenomatous Polyposis (FAP) is an autosomal dominant polyposis syndrome characterized by varying degrees of penetrance.[1] The primary genetic defect associated with this disorder is a germline mutation in the adenomatous polyposis coli (APC) gene. [11]

[12] Clinical manifestations and diagnosis of familial adenomatous polyposis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): ... performed in individuals at-risk for FAP who have either not undergone genetic evaluation or have indeterminate genetic test results. [13]

Treatment Options for Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of numerous polyps in the colon and rectum. If left untreated, it can lead to colorectal cancer. Fortunately, various treatment options are available to manage FAP.

Medications

Several medications have been investigated as potential treatments for FAP:

• Celecoxib: A COX-2 inhibitor that has shown promise in reducing the number of polyps in patients with FAP [1][6]. Studies suggest that celecoxib can decrease the size and number of adenomatous polyps, potentially delaying the onset of colorectal cancer [9].
• Metformin: This medication has been found to be safe and effective in treating FAP, possibly by modulating the intestinal flora [8].

Surgery

In addition to medications, surgery is often necessary to treat FAP:

• Colectomy: The surgical removal of the colon and rectum may be required to prevent colorectal cancer [3].
• Ileal pouch-anal anastomosis (IPAA): A type of colectomy that involves creating a pouch from the ileum (the last part of the small intestine) to serve as a reservoir for stool [4].

Combination Therapy

In some cases, combination therapy may be used:

• Erlotinib and sulindac: This combination has been shown to decrease the number of polyps in patients with FAP [5].
• Celecoxib and chemotherapy: In some instances, a combination of celecoxib and chemotherapy may be prescribed to reduce the number of polyps [1].

It's essential to note that each patient's situation is unique, and treatment decisions should be made in consultation with a healthcare professional.

References:

[1] Context 1: Jun 30, 2021 [3] Context 3: Treatment of familial adenomatous polyposis (FAP) and other colorectal conditions will usually involve a form of colorectal surgery. [4] Context 4: Apr 16, 2019 — These agents are used to reduce the number and the size of adenomatous polyps that remain in the rectum or ileal pouch after colectomy in patients with FAP. [5] Context 5: Mar 14, 2018 — In people with familial adenomatous polyposis, or FAP, a combination treatment of erlotinib (Tarceva) and sulindac (Aflodac) decreased the ... [6] Context 6: Drugs used to treat Familial Adenomatous Polyposis ; Generic name: celecoxib systemic; Drug class: cox-2 inhibitors; For consumers: ... [8] Context 8: by L Zhou · 2024 · Cited by 2 — One-year metformin therapy for FAP is safe and effective, potentially mediated by modulating the intestinal flora. [9] Context 9: by CA Burke · 2020 · Cited by 63 — Celecoxib, a COX-2 inhibitor, at a high dosage was briefly approved for the treatment of familial adenomatous polyposis on the basis of a 28% ...

Differential Diagnoses for Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis (FAP) is a rare inherited cancer predisposition syndrome characterized by the development of hundreds to thousands of precancerous colorectal polyps. To accurately diagnose FAP, it's essential to differentiate it from other conditions that cause multiple polyps. Here are some differential diagnoses for FAP:

• Peutz-Jeghers Syndrome: This is a rare genetic disorder characterized by the growth of polyps in the gastrointestinal tract and an increased risk of certain cancers. While both FAP and Peutz-Jeghers syndrome involve the development of polyps, they have distinct clinical features [5].
• Neurofibromatosis Type 1 (NF1): NF1 is a genetic disorder that affects the nervous system and causes the growth of non-cancerous tumors. While NF1 can cause multiple polyps in some cases, it's not typically associated with the development of hundreds to thousands of precancerous colorectal polyps [1].
• Cronkhite-Canada Syndrome: This is a rare condition characterized by the growth of multiple polyps in the gastrointestinal tract and an increased risk of certain cancers. While Cronkhite-Canada syndrome shares some similarities with FAP, it's typically associated with a more complex clinical presentation [1].
• MUTYH Attenuated FAP (MAP): This is a rare genetic disorder caused by mutations in the MUTYH gene. It's characterized by the development of multiple polyps and an increased risk of certain cancers. While MAP shares some similarities with FAP, it has distinct clinical features [2][9].
• Gastric Adenocarcinoma and Proximal Polyposis (GAPP): This is a rare condition characterized by the growth of multiple polyps in the stomach and an increased risk of gastric adenocarcinoma. While GAPP shares some similarities with FAP, it's typically associated with a more complex clinical presentation [3].

These differential diagnoses highlight the importance of accurate diagnosis and genetic testing to distinguish FAP from other conditions that cause multiple polyps.

References:

[1] Apr 16, 2019 — Differential Diagnoses. Cowden Disease (Multiple Hamartoma Syndrome) · Cronkhite-Canada Syndrome · Neurofibromatosis Type 1 · Peutz-Jeghers ...

[2] by E Half · 2009 · Cited by 918 — Genetic differential diagnosis-MUTYH, in brief​​ MUTYH mutation causes the polyposis condition known as MUTYH Attenuated FAP (MAP). It is recessively inherited ...

[3] APC-associated polyposis conditions include (classic or attenuated) familial adenomatous polyposis (FAP) and gastric adenocarcinoma and proximal polyposis ...

[5] Jul 29, 2020 — Familial adenomatous polyposis must be differentiated from other diseases that cause multiple polyps, such as Peutz–Jeghers syndrome, juvenile ...

[7] by DC Chung · Cited by 7 — This topic will review the genetics, clinical manifestations, and diagnosis of FAP and its variants (attenuated FAP [AFAP], and gastric ...