Peutz-Jeghers Syndrome

What is Peutz-Jeghers syndrome (PJS)?

Peutz-Jeghers syndrome (PJS) is a condition that causes polyps to form inside your body and dark-colored spots to appear on your face, hands, feet and elsewhere. Both the polyps and the spots are benign (noncancerous). Still, having PJS substantially increases your cancer risk.

The spots (mucocutaneous hyperpigmentation) appear in children with PJS but eventually fade over time. The polyps (hamartomatous polyps) usually form in your gastrointestinal (GI) tract. They’re most common in your small intestine, stomach and large intestine (colon). But they can also form outside of your digestive tract, in places like your kidneys, bladder, lungs and nose. The polyps can transform into cancer and cause complications that need treatment.

Your healthcare provider will regularly screen for cancer and high-risk polyps if you have PJS.

How common is Peutz-Jeghers syndrome?

Researchers don’t know the exact number of cases, but it’s relatively rare. They estimate that Peutz-Jeghers syndrome affects anywhere from 1 in 25,000 to 1 in 300,000 people.

What are the symptoms of Peutz-Jeghers syndrome?

PJS causes dark-colored spots (in children) and hamartomatous polyps (in children and adults).

Children with Peutz-Jeghers syndrome develop blue-gray or brown spots that may be mistaken for freckles. They usually show up around ages 1 and 2 and fade once your child reaches their late teens. They’re usually 1 millimeter (tip of a sharpened pencil) to 5 millimeters (surface of a pencil eraser). They can appear on various body parts, including:

• On or around your lips (most common).
• Inside your mouth.
• Nose.
• Eyes.
• Fingers.
• Palms of your hands.
• Soles of your feet.
• Anus (butthole).

Other symptoms relate to having polyps in your GI tract (especially your intestines or stomach) or experiencing complications related to the polyps. These symptoms usually appear when you’re between 10 and 30 years of age. Signs and symptoms of polyps include:

• Stomach pain.
• Nausea and vomiting.
• Gastrointestinal bleeding.
• Blood in your stool (poop).
• Anemia (excessive blood loss can lower your iron levels.)

What causes Peutz-Jeghers syndrome?

Most people with Peutz-Jeghers syndrome have a mutation (change) in one copy of the STK11 gene. STK11 is a tumor suppressor gene. A tumor suppressor gene works like a light switch for cell growth. If the gene isn’t working as it should, it’s like someone left the light on. With nothing to turn it off, the cells just keep growing. They stick together and form clumps of cells (tumors).

Up to 80% of people with PJS have a family history of the gene mutation and inherited it from one of their biological parents. The other 20% have the gene mutation but don’t have a family history, or they don’t have the gene mutation at all. People with a mutated STK11 gene without a family history of PJS likely acquired the mutation at some point. Scientists are unsure what causes PJS when there isn’t an STK11 mutation.

How is Peutz-Jeghers syndrome inherited?

Usually, a biological parent passes down the mutated PJS gene to their child. The mutation that causes PJS is inherited in an autosomal dominant pattern.

It works like this. Both parents pass on a single copy of the STK11 gene to their child. You only have to inherit a mutated gene from one of your parents to be at increased risk of PJS symptoms and complications.

If you have the mutation, there’s a 50/50 chance you’ll pass it along to your child.

What are the complications of PJS?

The most serious complication is cancer. Researchers estimate that your lifetime risk of developing cancer is as high as 93% if you have PJS. Your healthcare provider will screen for cancer regularly to catch and treat it early, when treatments are most effective.

Other complications include:

• Intussusception of the small bowel: A condition where your small intestine turns itself inside out. This happens when your small intestine tries to pass a large polyp. As many as 69% of people with PJS experience intussusception.
• Small bowel obstruction (blockage): The polyps can block your small intestine. Up to 50% of people with PJS experience a small bowel obstruction requiring surgery before they turn 20.
• Gastrointestinal bleeding: The polyps can place pressure on the tissue in your GI tract, causing bleeding.
• Iron-deficiency anemia: Blood loss can deplete your iron stores and cause anemia.

Females can develop sex-cord tumors of the ovary and a rare, aggressive type of cervical cancer, called adenoma malignum. These tumors can cause irregular periods or early puberty.

Males can develop tumors of the sex-cord and Sertoli-cell type of the testicles. These tumors can cause breast development (gynecomastia) and early puberty. Their bones may develop faster than normal (advanced skeletal age), and they may be below-average height.

What are the cancer risks associated with Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome (PJS) increases your risk of developing cancer in your GI tract and other organs. The average age of cancer diagnosis with PJS is 42. The most common types of cancer that people with PJS develop and the percentage of people who develop it are as follows:

• Colorectal cancer: Up to 40%.
• Breast cancer: 30% to 50%.
• Pancreatic cancer: 11% to 36%.
• Stomach cancer: Up to 30%.
• Ovarian cancer: 20%.
• Lung cancer: 15%.
• Small bowel cancer: Up to 13%.
• Cervical cancer: 10%.
• Uterine cancer: Less than 10%.
• Testicular cancer: Less than 10%.
• Esophageal cancer: 2%.

How is Peutz-Jeghers syndrome diagnosed?

Most people diagnosed with PJS see their healthcare provider because they have symptoms of a bowel obstruction or intussusception related to polyps. The average age people get diagnosed with PJS is 23. To diagnose PJS, providers look for:

• A family history of PJS.
• Dark-colored spots.
• Polyps in your GI tract.

They’ll also test for the mutation in your STK11 gene.

What tests will be done to diagnose this condition?

Your provider may perform various imaging procedures, including ones that use a scope to look for polyps inside your digestive tract. Tests may include:

• Colonoscopy: An examination of your large intestine.
• Upper endoscopy: An examination of your food tube (esophagus), stomach and the upper part of your small intestine.
• Capsule endoscopy: An examination of your digestive tract that involves swallowing a capsule with a tiny camera that takes pictures as it moves through your system.

They may take a blood sample to check for signs of iron-deficiency anemia. They can perform genetic tests on your blood to check for the STK11 gene mutation.

How is Peutz-Jeghers syndrome (PJS) treated?

Your healthcare providers will watch your organs to monitor for cancer and prevent polyp-related complications.

They can remove polyps in your colon during a colonoscopy. They can biopsy and remove polyps in your stomach and duodenum (part of your small intestine) if necessary. Your provider can often view and remove polyps deeper down in your small intestine during a balloon-assisted enteroscopy.

Sometimes, you may need surgery to remove polyps. Surgeons can usually remove the polyps one by one without needing to remove segments of your intestines.

What screenings will I need?

The timeline for recommended screenings goes like this:

• CT/MRI enterography or video capsule endoscopy:
  • Start at age 8 to 10 years and repeat every two to three years if there are polyps. If there aren’t any polyps, wait to restart screening at age 18 and perform every two to three years after.
  • Start at age 12 at the latest and repeat annually if there are polyps or every two to three years if there aren’t any polyps.
• Upper endoscopy:Start at age 12 and repeat annually if there are polyps or every two to three years if there aren’t any polyps.
• Magnetic resonance cholangiopancreatography or endoscopic ultrasound: You’ll need one every one to two years, starting at age 25 to 30 years.

Women

• Breast exams by a healthcare provider twice a year beginning at age 25 years.
• Annual mammogram and breast MRI beginning at age 25 years.
• Annual pelvic exams and Pap smears beginning between age 18 and 20 years.
• Annual transvaginal ultrasound beginning between age 18 and 20 years (optional).

Men

• Annual testicular exam and watching for feminizing changes (like breast development) beginning at age 10.

Can Peutz-Jeghers syndrome be prevented?

There’s nothing you can do to prevent developing PJS because it’s usually inherited.

You can inform your family members about your diagnosis and encourage them to get genetic counseling. The evaluation includes genetic testing for the PJS gene mutation. If they have a mutated STK11 gene, they’ll receive recommendations for cancer prevention and staying healthy.

If you have PJS, you have a 50/50 chance of passing the gene mutation to your child. But there are options to reduce your risk.

For example, preimplantation genetic diagnosis (PGD) may be an option if you use in vitro fertilization (IFV) to get pregnant. PGD tests embryos (fertilized eggs) for the gene mutation.

Still, PGD is a complex and costly procedure. Review your options with a genetic counselor.

What is the outlook for Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome (PJS) can’t be cured. It’s a life-long condition that you can pass onto your children. If you have PJS, you’ll need to be checked frequently for polyps. They can transform into cancer or cause a blockage that could require surgery.

What questions should I ask my healthcare provider?

Questions to ask include:

• What screenings will I need, and how often?
• What symptoms should I contact you about?
• What treatments will I need?
• What specialists will I need to work with?
• How will having PJS affect my plans for pregnancy?