Familial Adenomatous Polyposis Subtypes

Familial adenomatous polyposis (FAP) is a hereditary condition characterized by the development of multiple polyps in the colon and rectum. It is caused by mutations in the adenomatous polyposis coli (APC) gene.

FAP can be further classified into several subtypes, each exhibiting distinct clinical features and genetic variations. Understanding these subtypes is crucial for accurate diagnosis, prognosis, and tailored management strategies. This article provides an overview of the subtypes of FAP based on recent research findings.

Classic FAP is the most common subtype and is characterized by the presence of hundreds to thousands of adenomatous polyps throughout the colon and rectum. It typically manifests during adolescence or early adulthood, leading to a high risk of colorectal cancer if left untreated.

Genetic analysis finds a pathogenic mutation in the APC gene in almost all affected individuals. The identification of this subtype allows for early screening and prophylactic colectomy, thereby reducing the risk of cancer development.

Attenuated FAP (AFAP) is a milder form of the condition, characterized by a smaller number of polyps (usually less than 100) and a later age of onset. AFAP may present in the third or fourth decade of life, and the risk of colorectal cancer is lower than in classic FAP, but is still substantial.

AFAP is caused by specific mutations in the APC gene that result in a partially functional protein. The identification of AFAP is essential, as it influences surveillance and management decisions. Regular colonoscopies are recommended to monitor polyp growth and detect any potential malignancy.

Gardner Syndrome is a rare variant of FAP characterized by colonic polyps as well as extracolonic manifestations. In addition to multiple polyps, individuals with Gardner Syndrome may develop benign tumors in various tissues, including the skin (epidermoid cysts and desmoid tumors), bones (osteomas), and soft tissues. Dental abnormalities, such as odontomas and supernumerary teeth, are also common.

Gardner Syndrome is caused by mutations within the APC gene, and other possible linked mutations which create the Gardner variant, and requires multidisciplinary management involving gastroenterologists, dermatologists, and orthopedic surgeons.

Turcot Syndrome is a rare subtype of FAP characterized by the development of colorectal polyps alongside central nervous system (CNS) tumors. The CNS tumors in Turcot Syndrome are predominantly medulloblastomas or glioblastomas. This subtype is caused by mutations in genes other than APC, such as mismatch repair genes (e.g., MLH1, MSH2).

The identification of Turcot Syndrome is crucial, as it necessitates specialized surveillance protocols for both colorectal and CNS tumors.

Patients who have undergone a colectomy with ileal pouch-anal anastomosis (IPAA) as part of FAP management may develop pouchitis, an inflammatory condition affecting the ileal pouch.

Pouchitis-associated with FAP is characterized by recurrent episodes of pouch inflammation, which can resemble ulcerative colitis. Genetic testing may reveal specific APC mutations associated with this subtype. Treatment often involves medical therapy with antibiotics and anti-inflammatory medications, but surgical interventions may be required in severe cases.

Untreated FAP patients have a shorter life expectancy, and regular colonoscopy and screening is recommended for individuals who have been identified with the disease. Accurate diagnosis and subtype classification are essential for appropriate surveillance, prevention, and treatment strategies. Genetic testing plays a vital role in confirming the subtype, allowing for personalized management plans tailored to each patient's specific needs.

This can begin as early as 10 to 12 years of age, and a polypectomy can be done during the screening colonoscopy to remove any polyps identified. In cases where the polyp load is uncontrollable, a colectomy is recommended to remove the colon and/or rectum. The colon can be completely removed, but in cases where a subtotal colectomy is done, constant surveillance to investigate the risk of developing rectal cancer should be conducted.

Other non-surgical treatments have limited effectiveness — drugs such as Sulindac can reduce the adenoma load by 50%, but cannot prevent a recurrence once the drug is discontinued.

Living with FAP is not easy, and the definitive treatment options are extensive and life- changing, but if there is a chance to eliminate the risk of developing colorectal cancer, the opportunity shouldn’t be disregarded. In the case of FAP, it is indeed better late than never.