The genetic inheritance of Peutz-Jeghers syndrome is .
USMLE® Step 2 style questions USMLE
An 11-year-old boy comes to the clinic for a consultation. For years, the patient reports freckles around his mouth and gums that have become increasingly bothersome. Physical examination shows melanocytic macules 1-5 mm in size around the mouth, lips, gums, eyes, hands, and feet. His medical history is noncontributory. Family history is positive for breast, pancreatic, and colon cancer. Which of the following is the most appropriate next step in managing this patient?
Peutz-Jeghers syndrome, named after Dr. Jan Peutz, who first described it, and Dr. Harold Joseph Jeghers, who later reported on it, is a rare autosomal dominant condition in which individuals develop polyps throughout their gastrointestinal tract, as well as dark spots called melanotic macules in their mouth, lips, genitalia, palms, and soles.
The large intestine is found in the abdominal cavity, which can be thought of as having two spaces - the intraperitoneal space and the retroperitoneal space.
The intraperitoneal space contains the first part of the duodenum, all of the small intestines, the transverse colon, sigmoid colon, and the rectum; the retroperitoneal space contains the distal duodenum, ascending colon, descending colon, and anal canal.
So the large intestines essentially weave back and forth between the intraperitoneal and retroperitoneal spaces.
Now, the walls of the gastrointestinal tract are composed of four layers.
The outermost layer is the called serosa for the intraperitoneal parts, and the adventitia for the retroperitoneal parts.
Next is the muscular layer, which contracts to move food through the bowel.
After that is the submucosa, which consists of a dense layer of tissue that contains blood vessels, lymphatics, and nerves.
And finally, there’s the inner lining of the intestine called the mucosa; which surrounds the lumen of the gastrointestinal tract, and comes into direct contact with digested food.
The mucosa has invaginations called intestinal glands or colonic crypts, and it’s lined with large cells that are specialized in absorption.
Peutz-Jeghers syndrome is caused by a mutation of the STK11 gene, which is a tumor suppressor gene that codes for a protein called STK11.
So without a functioning STK11 gene, the gastrointestinal cells are more likely to accumulate mutations and start dividing faster than usual - ultimately giving rise to polyps.
These polyps are benign outgrowths that arise along the gastrointestinal tract, mostly in the small intestine, but also in the stomach and large intestine as well.
Some polyps then go on to accumulate additional mutations in other tumor suppressor genes like the K-ras gene and p53 gene, and at that point they might evolve into cancer.
The chance for any single polyp to develop into cancer is generally quite low, but with people with many polyps, like those suffering from juvenile polyposis syndrome, the risk for cancer becomes significant.
The STK11 gene is expressed in a number of tissues, so individuals with Peutz-Jeghers syndrome also have an increased risk of developing extraintestinal cancers without polyps, such as pancreatic, breast, lung, ovarian, uterine, and testicular cancer.
Polyps can be classified by their gross appearance.
Some are flat, which means that they don’t protrude into the lumen from the mucosa.