Familial Adenomatous Polyposis (FAP)

FAP is the most common polyposis syndrome.

Classical FAP

Classical familial adenomatous polyposis is an autosomal dominant inherited syndrome characterized by the presence of hundreds to thousands of adenomas (polyps) throughout the large bowel. The penetrance in FAP is close to 100%. Nearly 80% of patients have kin with FAP. However, 10-30% of patients represent spontaneous mutation.

Colorectal Phenotype

Affected individuals are healthy at birth. During the second or third decade of life, however, adenomas begin to develop until the colon and rectum are covered by hundreds to thousands of growths. If left untreated, one or more of these adenomas will inevitably develop into colorectal adenocarcinoma at a mean age of 40 years.

Offspring of an affected individual will have a 50% chance of inheriting and developing the disease. Pre-symptomatic diagnosis by screening of these at-risk family members and prophylactic (preventive) colectomy of affected individuals are effective ways to prevent malignant transformation, and thus reduce mortality and morbidity from colorectal cancer in FAP individuals.

Extracolonic Phenotype

Apart from colorectal involvement, patients with FAP are at risk for a broad spectrum of extracolonic manifestations (ECM) involving all three embryonic cell lineages.

Some ECMs, including epidermoid cyst, osteoma, dental odontoma, congenital hypertrophied retinal pigmented epithelium (CHRPE) and gastric fundic gland polyps, have benign course. In the era prior to genetic testing, CHRPE represents a very useful diagnostic biomarker to allow FAP diagnosis before the appearance of colorectal adenomas.

Certain ECMs have, however, potentially life-threatening consequences. Upper gastrointestinal malignancy (especially duodenal adenocarcinoma) and desmoids tumours represent the two major causes of morbidity and mortality in FAP patients who received prophylactic colectomy. Therefore, regular surveillance for ECMs is recommended. Other associated malignancies include pancreatic, biliary tree, small intestine, thyroid, adrenal and brain tumours.

Attenuated Phenotype

A milder form of the syndrome, called Attenuated FAP (AFAP) is characterized by adenomas developing later in life and these adenomas are predominantly on the right side of the colon.

FAP Genotype

FAP is caused by germline mutation of the Adenomatous Polyposis Coli (APC) gene located on the long arm of chromosome 5 (5q21-22). Germline mutation usually results in a premature stop codon signaling termination of transcription and formation of a truncated and functionally inactive protein.

Identification of the APC gene in the early 90s has allowed the characterization of disease-causing mutation in an FAP patient. Majority of the germline mutation occur between codons 1000 and 1600 which is referred to as the “mutation cluster zone”. AFAP-associated mutations have been shown to be located in specific regions of the APC gene.

In recent years, it is found that mutations in the MYH gene cause an autosomal recessive form of familial adenomatous polyposis (also called MYH-associated polyposis). Such mutations account for <5% of all adenomatous polyposis families reported to date. For these individuals, mutations in both copies of the MYH gene result in the polyposis phenotype.

Clinical and Molecular Diagnosis

For the majority of patients, clinical diagnosis is obvious except for the attenuated form.

With the advance of technology, molecular genetic analysis by sequencing and MLPA can allow identification of germline APC gene mutation in more than 80% of patients with a clinical diagnosis of FAP.

Screening of Family Members

Once an FAP patient is diagnosed, screening should be offered to all at-risk first-degree relatives within the family. Pre-symptomatic diagnosis by screening has been shown, both in Hong Kong and other countries, to decrease colorectal cancer rate and its related mortality significantly in these high-risk individuals.

In families with identifiable pathogenic germline APC mutation (from surviving index patient), predictive genetic testing could be offered to at-risk first-degree relatives above the age of 12 with an accuracy rate approaching 100%. Family members with a negative result can be discharged from further screening. For family members who are detected to be mutated gene carriers, genetic counseling and rigorous endoscopic surveillance are recommended to recognize the phenotype early to allow timely appropriate clinical management.

In those families in which genetic testing is not possible (due to no surviving index patients) or uninformative (due to no identifiable mutation), all at-risk relatives above the age of 12 years will be offered the traditional biennial lower endoscopic surveillance.


There is no known medical cure for FAP.

Prophylactic Colectomy

Due to the large number of adenomas in the large bowel and the high cancer risk, surgical resection is the only feasible preventive strategy against colorectal cancer and it should be performed as early as possible to maximize outcome.

There are several types of surgical resection available for FAP. The choice depends on the patient’s preference on aftercare and the distribution of polyposis in the large bowel. In each of the following operations, the patient’s individual needs and circumstances are considered:

  1. Colectomy and ileorectal anastomosis (IRA) – The removal of the colon, leaving 10-15 cm of the rectum. The last part of the small bowel (ileum) is joined, or anastomosed, to the rectum. Since the rectum remains, the patient must be sigmoidoscoped lifelong at regular intervals (usually every 6 months) to ensure that no new adenomas develop. If the remaining rectum contains only a few adenomas, these can be removed or destroyed through the sigmoidoscope. This operation is not suggested if a patient already has cancer, if there are too many rectal adenomas, or if the patient will not return for ongoing examination after surgery.
  2. Restorative proctocolectomy (pelvic pouch) – The excision of the colon, upper part of the rectum and lining of the lower part of the rectum leaving the sphincter muscles controlling the urge for a bowel movement. A new rectum, or pouch, is created from the ileum, brought down into the pelvis, and then joined to the anus. Time is needed for the area to properly heal and ensure good function of the pouch. Therefore, a temporary opening (stoma) is made from the ileum to the outside of the abdomen. This surgically created opening is called an ileostomy which means that an external appliance is worn to collect waste products. After about three months, a second shorter operation is required to close the ileostomy. Patient must continue medical follow-up of their pouch as part of their preventive health care. This technical procedure is not recommended for all patients with FAP and should be performed by experienced surgeons. A pelvic pouch should not be done in patients who already have, or subsequently develop, a rectal cancer.
  3. Proctocolectomy – The removal of the entire colon and rectum. A permanent ileostomy is formed, usually to the right and below the umbilicus (navel) so that waste products can pass into an external appliance. This operation may be suggested if there are too many adenomas in the rectum to be controlled by other methods or if there is rectal cancer.

Post-colectomy Surveillance

After prophylactic colectomy, FAP patients should continue to have lifelong regular surveillance for the remaining at-risk gastrointestinal mucosa:

  1. Residual rectum – For those who had colectomy and ileorectal anastomosis (IRA), the remaining rectum require regular sigmoidoscopic surveillance and ablation of residual and new rectal adenomas at six monthly intervals. Failure to control the rectal polyps by endoscopic indicates the need for completion proctectomy to prevent rectal cancer development.
  2. Pelvic pouch – It is increasingly recognized that polyposis can develop in the pelvic pouch with a theoretical risk of malignant transformation. Therefore, these patients should be subjected to regular endoscopic surveillance. Upon identification, pouch adenomas can be controlled using a combination of endoscopic ablation and drug treatment.
  3. Upper gastrointestinal tract – Upper gastrointestinal tract surveillance should be performed using a combination of end-view gastroscope and side-view duodenoscope with the aim of ablating any worrisome lesions to prevent duodenal adenocarcinoma. The surveillance interval is usually every 2-3 years; yet, the intervals may be shortened in those with more severe form of duodenal polyposis.