Familial Polyposis of the Colon

Synonyms: familial adenomatous polyposis (FAP), familial polyposis coli.

Familial polyposis of the colon causes widespread development of adenomas in the colon and rectum. The number of polyps can range from no detectable polyps at colonoscopy to more than 7,000 seen on resected specimens of bowel. The polyposis predominantly affects the left colon (80-90%).¹

Gardner's syndrome is characterised by colonic polyposis with osteomas and soft tissue tumours. Turcot's syndrome is the association of colonic polyposis and tumours of the central nervous system.² In 1951 Gardner described the occurrence of FAP with the extracolonic manifestations of desmoids, osteomas and epidermoid cysts.

• The incidence of familial polyposis of the colon is between 1 in 8,300 and 1 in 14,025 live births.³
• Colonic polyps begin developing at a mean age of 16 years (range 7-36 years).²
• Familial polyposis syndromes have autosomal dominant inheritance with almost complete penetrance but marked variation in expression.⁴ Mutations of the APC gene on chromosome 5 are thought to be responsible.⁵
• The location of the mutation on the gene is thought to influence the nature of the extracolonic manifestations.³

• Adenomas usually begin to develop during the second decade of life.
• Unfortunately it often presents with colorectal cancer.
• The median age at diagnosis is 40.⁵

Symptoms

• Patients are often asymptomatic, but may present with rectal bleeding, diarrhoea, abdominal pain and mucous discharge.³
• Obstruction may cause constipation, vomiting and peritonitis.
• Dental abnormalities may cause jaw pain.
• Gastric polyps may cause epigastric pain or bleeding.
• Duodenal polyps may cause pain, bleeding or obstructive jaundice.
• Polyps in the ileum may cause obstruction.
• Thyroid carcinoma may present as a neck mass, pain, hoarseness and features of hypothyroidism or hyperthyroidism.

Signs

• Rectal polyps or masses.
• Other commonly associated features:⁵
  • Congenital hypertrophy of the retinal pigment epithelium (CHRPE) - evaluated by slit-lamp examination and indirect ophthalmoscopy - which can be an useful early clue as to whether the patient is a carrier of the APC gene.
  • Dental problems - supernumerary teeth, odontomas, non-erupted teeth.
  • Epidermoid cysts.
  • Desmoid tumours or osteomas (skull, endosteal and exosteal osteomas).
  • Thyroid masses.

• Full blood count.
• Carcinoembryonic antigen testing: raised levels may indicate colorectal carcinoma.
• Liver function tests to evaluate possible metastasis.
• Thyroid function tests.
• Faecal occult blood.
• CT or MRI scan of the abdomen and pelvis.
• Dental X-rays, chest X-ray and skull X-ray (for jaw lesions, osteomas, supernumerary teeth).
• Colonoscopy with biopsies: investigation of choice for diagnosis.
• Upper gastrointestinal endoscopy: for evaluation of gastric and duodenal polyps.
• Genetic testing: for the APC gene and its mutation. Prenatal testing is possible if a disease-causing mutation is identified in an affected family member.

Other hereditary polyposis syndromes:⁴

• Adenomatous polyposis syndromes, e.g. Turcot's syndrome
• Hamartomatous polyposis syndromes, e.g. Peutz-Jeghers' syndrome, juvenile polyposis and Cowden's disease

The majority of patients have one or more extracolonic features.^5,6 Extracolonic features include:³

• Malignant tumours:
  • Duodenal
  • Pancreatic
  • Thyroid
  • Brain (medulloblastoma)
  • Hepatoblastoma
• Nasopharyngeal angiofibromas
• Osteomas
• Radiopaque jaw lesions
• Supernumerary teeth
• Lipomas, fibromas, epidermoid cysts
• Desmoid tumours
• Gastric adenomas
• Duodenal, jejunal and ileal adenomas

Screening by flexible sigmoidoscopy with biopsy of polyps for histological diagnosis confirms the condition and allows surgery before the age of 20.

• A regression of polyps and biochemical markers has been reported with cyclo-oxygenase inhibitors. There is evidence that low-dose aspirin significantly reduces the recurrence of adenomatous polyps after 1 to 3 years.⁷ Sulindac is recommended in patients with rectal polyps following total colectomy.
• Tamoxifen has also been recommended.
• Sulindac, tamoxifen, or a combination of both, are recommended for desmoid polyps of the abdominal wall or for extra-abdominal manifestations of the disease.

Surgical

The types of surgery are:⁸

• Proctocolectomy with ileostomy
• Total colectomy with ileorectal anastomosis
• Restorative proctocolectomy with ileo pouch anal anastomosis is the main surgical treatment for patients with FAP.^9,10,11

Complications secondary to polyps lining the colon include:

• Gastrointestinal haemorrhage.
• Gastrointestinal obstruction.
• Malignant change (if prophylactic colectomy is not performed). The risk of colorectal cancer increases with the number of polyps:
  • By age 35 years, 95% of affected individuals have polyps and, without colectomy, colon cancer is inevitable.²
  • The mean age of colon cancer diagnosis in untreated individuals is 39 years (range 34-43 years).²
  • Patients with more than 1,000 polyps have been proven to have 2.3 times the cancer risk compared to patients with fewer than 1,000 polyps.
  • The cancer risk increases 2.4 times for every 10 years of polyps.¹

• Colon cancer will develop in all affected individuals unless prophylactic colectomy is performed.
• After total colectomy with ileorectal anastomosis, the recurrence rate is 30% after 20 years and 45% after 30 years.

Screening family members by flexible sigmoidoscopy confirms or eliminates the diagnosis.