Familial adenomatous polyposis (FAP)

Definition

Familial adenomatous polyposis (FAP) is an autosomal dominant disease in which 100 or more adenomatous polyps carpet the colon and rectum. In the natural course, nearly every affected person develops colon cancer before the age of 40. In addition, benign and malignant manifestations occur outside the large bowel; this combination was formerly called Gardner syndrome.

Classification

• Classic FAP: more than 100 colorectal polyps at colonoscopy
• Attenuated FAP (AFAP) or oligopolyposis: 10–99 synchronous adenomas, fewer than 100 at presentation, also inherited in an autosomal dominant pattern; the polyps tend to be located in the proximal colon

Occurrence & epidemiology

FAP affects about 1 in 10,000 people. Polyps are present in 50% of affected individuals by age 15 and in 95% by age 35.

Aetiopathogenesis

Genetics and manifestations

• Genetics: APC gene autosomal dominant.
• Classic FAP: > 100 colorectal adenomas from adolescence.
• Attenuated FAP: fewer polyps, later manifestation.
• Extracolonic manifestations: desmoid tumors + duodenal adenomas + CHRPE + osteomas (Gardner).

Clinical features

Many affected individuals have no symptoms; rectal bleeding, usually occult, is common.

Extracolonic manifestations:

• benign: desmoid tumors, osteomas of the skull or mandible, sebaceous (epidermoid) cysts, adenomas in other parts of the gastrointestinal tract
• increased cancer risk: duodenum (5–11%), pancreas (2%), thyroid (2%), brain (medulloblastoma in less than 1%) and liver (hepatoblastoma in 0.7% of children under 5 years)

Diagnosis

• Colonoscopy: finding more than 100 polyps establishes the diagnosis; the characteristic lesions can already be recognized at sigmoidoscopy, while colonoscopy also detects more proximal cancers
• Genetic testing to identify the specific mutation; then targeted testing of first-degree relatives
• Offspring of affected individuals: screening for hepatoblastoma
• In attenuated FAP, complete colonoscopy is particularly important because the polyps tend to be more proximal

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Familial Adenomatous Polyposis
2. MSD Manual Professional: Polyps of the Colon and Rectum
3. StatPearls: Familial Adenomatous Polyposis
4. NCI PDQ: Genetics of Colorectal Cancer (Health Professional Version)

Cross-references