Familial Adenomatous Polyposis (FAP)

What FAP is

The APC gene normally acts as a brake on cell growth in the bowel lining. Each person has two copies. People with FAP inherit one faulty copy, so every cell has only one working brake. When the second copy is damaged in a bowel cell, which happens frequently over time, that cell forms an adenoma, a polyp that can become cancer.

Types of FAP

MUTYH-associated polyposis (MAP) looks like attenuated FAP but is inherited recessively (from both parents) and caused by a different gene.

Symptoms

Many people have no symptoms until polyps are numerous or cancer develops. Possible signs:

• rectal bleeding or blood in stool
• diarrhea or change in bowel habit
• abdominal pain
• tiredness from iron deficiency anemia
• unexplained weight loss

Features outside the colon

• Duodenal and ampullary polyps: almost universal; duodenal cancer is a leading cause of death after colectomy.
• Stomach fundic gland polyps: common, usually benign.
• Desmoid tumors: non-spreading but locally aggressive growths, often in the abdomen or abdominal wall, frequently after surgery.
• Congenital hypertrophy of the retinal pigment epithelium (CHRPE): harmless pigmented spots seen on eye examination.
• Osteomas (benign bone growths), dental abnormalities, epidermoid cysts.
• Thyroid cancer, mostly in young women.
• Hepatoblastoma: a liver cancer in young children.
• Brain tumors (medulloblastoma) rarely.

Inheritance

FAP is autosomal dominant: each child of an affected parent has a 50% chance of inheriting it. About 25% of people with FAP have a new mutation with no family history. Genetic counseling is recommended for all families.

Diagnosis

• Genetic testing for APC mutations (and MUTYH) in people with many adenomas or a family history. Once the family mutation is known, relatives can be tested precisely.
• Colonoscopy or sigmoidoscopy: shows the number and size of polyps; biopsies confirm adenomas.
• Upper endoscopy with a side-viewing scope: to check the duodenum and ampulla.
• Eye examination for CHRPE (supportive).

Screening for at-risk family members

• Children of affected parents are usually offered genetic testing around age 10 to 12.
• Mutation carriers start colonoscopy or flexible sigmoidoscopy every 1 to 2 years from about age 10 to 12.
• Attenuated FAP screening starts later, in the late teens, with colonoscopy.
• Upper endoscopy usually begins around ages 20 to 25.
• Thyroid ultrasound is often recommended, beginning in the late teens.
• Some centers screen young children for hepatoblastoma with liver ultrasound and alpha-fetoprotein.

Treatment

Preventive surgery

Surgery to remove the colon is the main way to prevent cancer. Timing depends on polyp number, size and appearance, usually in the late teens or early twenties.

• Total colectomy with ileorectal anastomosis (IRA): removes the colon but keeps the rectum; needs regular rectal checks because polyps can form there.
• Proctocolectomy with ileal pouch-anal anastomosis (IPAA): removes colon and rectum and creates an internal pouch from the small intestine; used for many rectal polyps.
• Proctocolectomy with permanent ileostomy: occasionally.

After surgery

• endoscopic surveillance of the remaining rectum or pouch every 6 to 12 months
• regular upper endoscopy; removal of duodenal polyps or surgery for advanced disease
• monitoring and treatment of desmoid tumors with medicines, observation or, rarely, surgery

Medicines

Some anti-inflammatory medicines have been studied to reduce polyp numbers but do not replace surgery or surveillance.

Outlook

With early diagnosis, timely colectomy and lifelong surveillance, most people with FAP avoid colorectal cancer and live into older age. The main remaining risks come from duodenal cancer and desmoid tumors, which is why follow-up never stops.

Frequently asked questions

What is familial adenomatous polyposis?

FAP is an inherited condition caused by a mutation in the APC gene. It causes hundreds to thousands of polyps in the colon and rectum, starting in the teens, and almost certainly leads to colorectal cancer without treatment. Preventive surgery and surveillance greatly reduce this risk.

Is FAP hereditary?

Yes. FAP is inherited in an autosomal dominant way, so each child of an affected parent has a 50% chance of inheriting the mutation. About a quarter of cases arise from a new mutation in someone with no family history.

When should screening start for FAP?

Children of a parent with FAP are usually offered genetic testing and, if positive, colonoscopy or sigmoidoscopy every 1 to 2 years from around age 10 to 12. Attenuated FAP screening starts later, in the late teens.

What is attenuated FAP?

Attenuated FAP is a milder form with fewer than 100 polyps, appearing later in life. Colorectal cancer risk is still high, but it typically develops later, around age 50 to 55. Some people can be managed with colonoscopy and polyp removal rather than early surgery.

Can you live a normal life with FAP?

Many people do. After preventive surgery, most adjust well, though bowel movements are more frequent. Lifelong check-ups of the rectum or pouch, duodenum and thyroid are essential. Many people with FAP work, have families and live long lives.