Juvenile polyposis syndrome

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Introduction0:00–0:17

In juvenile polyposis syndrome, young children develop multiple polyps throughout the gastrointestinal tract, especially in the large intestine, and unfortunately some of those polyps can develop into colon cancer at some point in their life.

Physiology0:17–1:34

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 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.

Pathology1:34–3:48

In juvenile polyposis syndrome there’s an autosomal dominant mutation in the SMAD4 gene, which encodes a protein that’s part of a pathway that induces apoptosis or programmed cell death.
Without a functioning SMAD4 gene, the gastrointestinal cells that mutate are more likely to escape having to undergo apoptosis, and instead they simply divide faster than usual - ultimately giving rise to polyps, which are benign outgrowths that arise along the gastrointestinal tract, mostly in the colon.
Some polyps then go on to accumulate additional mutations in other tumor suppressor genes like the 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 people with juvenile polyposis syndrome have so many polyps, that they have a higher risk of cancer because the chance that a single one might turn into a cancer is significant.
In fact, many individuals with juvenile polyposis syndrome develop cancer by age 45. Usually it’s colorectal cancer, but the SMAD4 gene is expressed in other tissues, and they sometimes develop cancers of the small intestine, stomach, and pancreas as well.
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.
People with juvenile polyposis syndrome develop hamartomatous polyps, sometimes just called hamartomas, and these are either sessile or pedunculated.
Some individuals with juvenile polyposis syndrome also have congenital malformations, like macrocephaly which is an abnormally large head, or hypotonia which is when there’s low muscle tone and strength.

Symptoms3:48–4:09

Individuals with juvenile polyposis syndrome often don’t have any symptoms; however, if a polyp becomes big enough to obstruct the intestine, it can cause abdominal pain and constipation.
Some polyps can also ulcerate and cause gastrointestinal bleeding, which can lead to iron deficiency anemia in the long run.

Diagnosis4:09–4:41

Diagnosis of juvenile polyposis syndrome typically requires colonoscopy, which is when a camera is inserted retrograde into the colon and rectum and takes pictures of abnormal looking polyps; and a biopsy.
The presence of hamartomas is key in making the diagnosis. In addition, fecal occult blood testing is often done to look for evidence of gastrointestinal bleeding.
Ultimately, genetic testing has to be done to look for a mutation in the SMAD4 gene. It’s important for individuals with juvenile polyposis syndrome to have frequent endoscopies to screen for colon cancer.

Treatment4:41–5:13

Some individuals also undergo prophylactic surgery, which means removing the part of the intestine that has hamartomas before they evolve into carcinomas.
In addition, these individuals also need to be monitored regularly for signs of cancer in other organs like the small intestines, stomach, and pancreas.
All right, as a quick recap, juvenile polyposis syndrome is an autosomal dominant condition caused by a mutation of the SMAD4 gene.

Review5:13–6:01

Generally, affected children start developing multiple hamartomas throughout the gastrointestinal tract, and are at high risk of developing colon cancer at some point in their lives.
For this reason, people with juvenile polyposis syndrome need regular endoscopic monitoring, and sometimes have prophylactic surgery.