Attenuated FAP

Attenuated Familial Adenomatous Polyposis (AFAP)

Attenuated Familial Adenomatous Polyposis (AFAP) is a hereditary colorectal cancer syndrome characterized by the development of fewer colorectal polyps than classic Familial Adenomatous Polyposis (FAP). AFAP is associated with a later onset of colorectal cancer compared to classic FAP.

Genetics

AFAP is caused by mutations in the APC gene, which is located on chromosome 5q21-q22. The APC gene is a tumor suppressor gene that plays a critical role in regulating cell growth and apoptosis. Mutations in this gene lead to the development of multiple adenomatous polyps in the colon and rectum.

In AFAP, mutations often occur at the 5' and 3' ends of the APC gene or in exon 9, which results in a milder phenotype compared to classic FAP. The inheritance pattern of AFAP is autosomal dominant, meaning that a single copy of the mutated gene inherited from an affected parent can cause the condition.

Clinical Features

Individuals with AFAP typically develop between 10 to 100 adenomatous polyps in the colon and rectum, compared to hundreds to thousands in classic FAP. The average age of polyp development is later, often in the third or fourth decade of life. The risk of colorectal cancer is also present, but it occurs at a later age than in classic FAP.

Extra-colonic manifestations of AFAP can include:

• Gastric fundic gland polyps
• Duodenal adenomas
• Osteomas
• Dental abnormalities
• Congenital hypertrophy of the retinal pigment epithelium (CHRPE)

Diagnosis

The diagnosis of AFAP is based on clinical criteria, family history, and genetic testing. Colonoscopy is used to identify and monitor the number of polyps. Genetic testing can confirm the presence of mutations in the APC gene.

Management

Management of AFAP involves regular surveillance and prophylactic measures to reduce the risk of colorectal cancer. Recommendations include:

• Regular colonoscopic surveillance starting in the late teens or early twenties
• Consideration of prophylactic colectomy if polyp burden becomes unmanageable
• Surveillance of the upper gastrointestinal tract for duodenal adenomas

Prognosis

With appropriate surveillance and management, individuals with AFAP can have a favorable prognosis. Early detection and removal of polyps can significantly reduce the risk of colorectal cancer.

Also see

• Familial Adenomatous Polyposis
• APC gene
• Colorectal cancer
• Hereditary nonpolyposis colorectal cancer