Makindo Medical Notes

Related Subjects: | Autosomal Dominant | Autosomal Recessive | X Linked Recessive

Patients with Familial Adenomatous Polyposis (FAP) often have congenital hypertrophy of the retinal pigmented epithelium.

About

• FAP accounts for 0.5-1% of all colorectal cancers, affecting approximately 1 in 10,000 people.
• It is inherited as an autosomal dominant defect.
• The average age for developing colorectal cancer is 39 years old.
• In attenuated FAP, the average age for colorectal cancer onset is 55 years.

Genetics

• FAP is usually due to mutations in the APC gene. It is inherited in an autosomal dominant pattern, meaning one altered gene copy in each cell is enough to cause the disorder. In most cases, an affected person has one parent with the condition.
• A variant of FAP is caused by mutations in the MUTYH gene, which is inherited in an autosomal recessive pattern. Both gene copies in each cell must carry mutations for the condition to manifest. Parents of an individual with the autosomal recessive form usually carry one mutated gene copy but show no symptoms.
• Colorectal cancer is seen in nearly 100% of those affected by FAP.

Aetiology

• The APC gene is located on chromosome 5q band 21 or 22.
• FAP involves the loss of one of the two Adenomatous Polyposis Coli (APC) genes.
• Hypertrophy of the retinal pigment layer, which may be detected in infancy, is often associated with FAP.
• The APC gene functions as a caretaker or "gatekeeper" gene, preventing uncontrolled cell growth.
• An attenuated form of the disease, known as attenuated familial adenomatous polyposis, is characterized by a delayed onset of polyp growth.
• Desmoid tumours are common in FAP and tend to recur after surgical removal.

Clinical Features

• The diagnosis of FAP typically requires the development of >100 colorectal polyps.
• FAP often presents in adolescence, with polyps forming in teenage years.
• If untreated, patients typically develop bowel cancer by the age of 40.
• Other features include dental cysts, jaw osteomas, and retinal pigmentation.
• Epidermoid cysts, desmoid cysts, and hamartomatous gastric polyps are also associated with FAP.

Investigations

• Surveillance colonoscopy reveals multiple non-malignant polyps. The number of polyps increases with age, and hundreds to thousands may develop in the colon.
• DNA studies can identify individuals with the genetic mutations responsible for FAP.

Management

• Regular surveillance colonoscopy should begin in teenage years to monitor for polyp formation.
• Elective surgery options include:
  • Panproctocolectomy with end ileostomy.
  • Colectomy and ileorectal anastomosis, with continued inspection and removal of rectal polyps.
  • Proctocolectomy with ileal pouch-anal anastomosis, which is now the preferred surgical option.
• Screen other family members for FAP to enable early detection and management.