Familial Polyposis of the Colon (Gardner's Syndrome)

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

Widespread development of adenomas in the colon and rectum. Gardner described the occurrence of familial adenomatous polyposis with the extracolonic manifestations of desmoids, osteomas, and epidermoid cysts in 1951. The number of polyps can range from no detectable polyps at colonoscopy to more than 7000 seen on resected specimens of bowel. The polyposis predominantly affects the left colon (80-90%).¹

The incidence is between 1 in 8,300 and 1 in 14,025 live births.²

It is due to autosomal dominant inheritance with almost complete penetrance but marked variation in expression.³ Mutations of the APC gene on Chromosome 5 are thought to be responsible. The location of the mutation on the gene is thought to influence the nature of the extracolonic manifestations.²

Adenomas usually begin to develop during the second decade of life - unfortunately usually presents with colorectal cancer in early adult life. Median age at diagnosis is 40.⁴

Symptoms

• Patients are often asymptomatic, but may present with rectal bleeding, diarrhoea, abdominal pain and mucous discharge.²
• 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 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
• Commonly associated other features:⁴
  • 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 tumors 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 for 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

Other hereditary polyposis syndromes:³

• Adenomatous polyposis syndromes, e.g. Turcot 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.^4,5 Extracolonic features include:²

• Malignant tumours:
  • Duodenal
  • Pancreatic
  • Thyroid
  • Brain (medulloblastoma)
  • Hepatoblastoma
• Nasopharyngeal angiofibromas
• Osteomas
• Radiopaque jaw lesions
• Supernumerary teeth
• Lipomas, fibromas, epidermoid cysts
• Desmoid tumors
• 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. Sulindac is recommended in patients with rectal polyps following total colectomy.
• Tamoxifen has also been recommended.
• Sulindac, tamoxifen, or a combination of both is recommended for desmoid polyps of the abdominal wall or for extra-abdominal manifestations of the disease.

Surgical

The types of surgery are:⁶

• Proctocolectomy with ileostomy
• Total colectomy with ileorectal anastomosis
• Proctocolectomy with ileal pouch anal anastomosis.^7,8

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.
  • Patients with more than 1000 polyps have been proven to have 2.3 times the cancer risk compared to patients with fewer than 1000 polyps. The cancer risk increases 2.4 times for every 10-year 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.