AssessmentsFamilial adenomatous polyposis
Familial adenomatous polyposis
USMLE® Step 1 style questions USMLE
A heterosexual couple comes to the genetic counselor’s office for prenatal counseling. The woman has no significant past medical history, and her family history is not notable for any cancers. The man has a history of prophylactic colectomy at the age of 16 after a colonoscopy revealed hundreds of polyps. His father died at the age of 39 due to colorectal cancer, but his mother has been healthy. The couple is worried their children may also inherit this condition. What is the probability that this couple’s first child will inherit the disease?
With familial adenomatous polyposis, or simply FAP, familial refers to the fact that the disease runs in the family, and adenomatous polyposis refers to the fact that people affected develop multiple polyps that arise from the glands in the large intestine, which includes the colon and the rectum.
Now, the walls of the gastrointestinal tract are composed of four layers.
The outermost layer is called serosa.
Then there’s the muscular layer, which contracts in a synchronized way to move food through the bowel.
Then there is the submucosa, which consists of a dense layer of tissue through which blood vessels, lymphatics, and nerves run and branch into the mucosa and the muscular layer.
The mucosa is organized as invaginations called the intestinal glands or colonic crypts, lined with large cells that are specialized in absorption.
Tumor suppressor genes stop cells from dividing uncontrollably.
But if the gene is mutated and the cell is without a functioning APC, the intestinal gland cells are more likely to accumulate mutations and start dividing faster than usual - ultimately giving rise to polyps, which are benign outgrowths of intestinal gland tissue.
Even though for any single polyp the chance that it evolves into cancer is generally quite low, polyps might accumulate additional mutations in other genes like the p53 gene (another tumor suppressor) or K-ras gene (a proto-oncogene), and with enough mutations, a cell might become completely unregulated and might start invading nearby tissue and become malignant.
Polyps can be classified by their gross appearance.
Some are flat, which means that they don’t protrude into the lumen and are flat up against the mucosa.
Some are pedunculated which means that they do protrude into the lumen and remain attached to the wall by a stalk, just like a mushroom.
And some are sessile which means that they also protrude into the lumen, but have their base firmly attached to the mucosa.
Under the microscope, the cells look like normal colonic mucosa cells.
There are three types of adenomas based on histology: tubular, with little hollow tubes within it, villous, with tiny tree-like branches, and tubulovillous, which look like a mix of the two with hollow tubes and tree-like branches.
Tubular adenomas are the most common type and have less malignant potential than villous adenomas, while tubulovillous adenomas have intermediate malignant potential.
Familial adenomatous polyposis (FAP) is a rare, autosomal dominant condition characterized by the development of many polyps in the colon and rectum. These polyps can become cancerous over time, leading to a high risk of developing colorectal cancer. Surgery is often recommended to remove the polyps and prevent cancer from developing.
FAP is caused by mutations in the adenomatous polyposis coli (APC) gene. This gene normally helps to suppress tumor growth in the colon. When it is mutated, this function is lost, resulting in an increased risk of developing tumors. FAP can be diagnosed through genetic testing.