Familial Adenomatous Polyposis

Overview

Familial Adenomatous Polyposis (FAP) is a hereditary condition characterized by the development of hundreds to thousands of polyps (adenomas) in the lining of the colon and rectum. If left untreated, these polyps have a nearly 100% risk of progressing to colorectal cancer, often by the age of 40. FAP is considered a major hereditary colorectal cancer syndrome and requires early diagnosis and intervention to prevent malignancy. In some cases, polyps may also develop in the stomach, duodenum, and other parts of the gastrointestinal tract.

Causes

FAP is caused by mutations in the APC gene (adenomatous polyposis coli gene), a tumor suppressor gene that normally helps control cell growth. The mutation leads to uncontrolled cell proliferation and polyp formation. FAP is inherited in an autosomal dominant pattern, meaning a person only needs one copy of the altered gene from one parent to develop the condition. In about 20-30% of cases, the mutation occurs spontaneously (de novo), with no family history.

Symptoms

Symptoms of FAP may not appear until adolescence or early adulthood, though polyp formation usually begins in the teenage years. Common symptoms include:

• Rectal bleeding: Blood in the stool due to polyp irritation or ulceration.

• Abdominal pain or cramping: Especially if polyps are numerous or large.

• Changes in bowel habits: Such as diarrhea or constipation.

• Unintended weight loss: In advanced cases or with cancer development.

• Anemia: Caused by chronic bleeding from polyps.

In addition to gastrointestinal symptoms, FAP may include extracolonic features such as desmoid tumors, osteomas (bony growths), epidermoid cysts, and congenital hypertrophy of the retinal pigment epithelium (CHRPE).

Diagnosis

Diagnosis of FAP involves a combination of clinical evaluation, family history, and genetic testing. Key diagnostic steps include:

• Colonoscopy: Direct visualization and biopsy of colonic polyps; hundreds to thousands of adenomas are typically seen.

• Genetic testing: Identification of mutations in the APC gene confirms the diagnosis.

• Flexible sigmoidoscopy: May be used for screening younger individuals in high-risk families.

• Upper endoscopy: To detect polyps in the stomach and duodenum.

• Family screening: Close relatives of an affected person should undergo genetic testing and surveillance starting in childhood or adolescence.

Treatment

The goal of treatment is to prevent colorectal cancer by removing the colon or controlling polyp growth. Treatment options include:

• Prophylactic colectomy: Surgical removal of the colon (often performed between ages 15 and 25) to prevent cancer. Options include:

  • Total proctocolectomy with ileal pouch-anal anastomosis (IPAA)

  • Subtotal colectomy with ileorectal anastomosis (IRA)

• Endoscopic surveillance: For patients who have not had surgery or have a remaining rectum after IRA.

• Medication: NSAIDs such as sulindac or celecoxib may help reduce polyp number and size but are not a substitute for surgery.

• Monitoring extracolonic manifestations: Includes regular upper GI endoscopy and imaging for desmoid tumors.

Prognosis

With timely diagnosis and surgical intervention, individuals with FAP can have a normal life expectancy. However, without treatment, nearly all individuals with classic FAP will develop colorectal cancer, often before the age of 40. Regular surveillance, family screening, and lifelong follow-up care are essential. Patients who undergo colectomy still require monitoring for extracolonic manifestations and potential polyp development in the remaining gastrointestinal tract.