Familial Adenomatous Polyposis
Familial adenomatous polyposis is a hereditary disorder causing numerous colonic polyps and resulting in colon carcinoma by age 40. Patients are usually asymptomatic but may have heme-positive stool. Diagnosis is by colonoscopy and genetic testing. Treatment is colectomy.
Familial adenomatous polyposis (FAP) is an autosomal dominant disease in which ≥ 100 adenomatous polyps carpet the colon and rectum. The disorder occurs in 1 in 8,000 to 14,000 people. Polyps are present in 50% of patients by age 15 yr, and 95% by age 35 yr. Cancer develops before age 40 in nearly all untreated patients.
Patients also can develop various extracolonic manifestations (previously termed Gardner syndrome), both benign and malignant. Benign manifestations include desmoid tumors, osteomas of the skull or mandible, sebaceous cysts, and adenomas in other parts of the GI tract. Patients are at increased risk of cancer in the duodenum (5 to 11%), pancreas (2%), thyroid (2%), brain (medulloblastoma in < 1%), and liver (hepatoblastoma in 0.7% of children < 5 yr).
Diagnosis of familial adenomatous polyposis is made by finding > 100 polyps on colonoscopy. Although the characteristic lesions of FAP can be recognized on sigmoidoscopy, colonoscopy is usually done to detect a more proximal cancer, which would require evaluation for metastases before treatment.
Diagnosed patients should have genetic testing to identify the specific mutation, which should then be sought in 1st-degree relatives. If genetic testing is unavailable, relatives should be screened with annual sigmoidoscopy beginning at age 12, reducing frequency with each decade. If no polyps are evident by age 50, screening frequency is then the same as for average-risk patients.
Children of parents with FAP may be screened for hepatoblastoma from birth to age 5 yr with annual serum alpha-fetoprotein levels and possibly liver ultrasound.
Colectomy should be done at the time of diagnosis. Total proctocolectomy, either with ileostomy or mucosal proctectomy and ileoanal pouch, eliminates the risk of colon and rectal cancer. If subtotal colectomy (removal of most of the colon, leaving the rectum) with ileorectal anastomosis is done, the rectal remnant must be inspected frequently; new polyps must be excised or fulgurated. Coxibs may inhibit new polyp formation. If new ones appear too rapidly or prolifically to remove, excision of the rectum and permanent ileostomy are needed.
After colectomy, patients should have upper endoscopic surveillance at periodic intervals. The 2015 American College of Gastroenterology's guidelines for genetic testing and management of hereditary GI cancer syndromes recommend doing upper endoscopy including duodenoscopy starting at age 25 to 30 yr and repeating surveillance every 6 mo to 4 yr depending on the stage of duodenal polyposis. Annual screening of the thyroid with ultrasound also is recommended.
Familial adenomatous polyposis (FAP) is an autosomal dominant disease in which ≥ 100 adenomatous polyps carpet the colon and rectum.
Nearly all patients develop colon carcinoma by age 40, so total proctocolectomy is usually done at time of diagnosis.
Patients have an increased risk of other cancers, particularly of the duodenum, and also the pancreas, thyroid, brain, and liver.
After treatment, patients are screened regularly for other cancers and development of polyps in the upper GI tract.
Children of parents with FAP may be screened for hepatoblastoma from birth to age 5 yr.