Peutz-Jeghers Syndrome

Approved by the Cancer.Net Editorial Board, 07/2016

What is Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome (PJS) is an inherited condition that puts people at an increased risk for developing hamartomatous polyps in the digestive tract as well as cancers of the breast, colon and rectum, pancreas, stomach, testicles, ovaries, lung, cervix, and other types listed below. Without appropriate medical surveillance, the lifetime risk of cancer in people with PJS may be as high as 93%. A hamartoma is a growth of normal-appearing tissue that builds up into a benign (noncancerous) tumor. In PJS, hamartomatous polyps often develop in the small and large intestine, and they can cause bleeding or other problems, such as an intestinal blockage.

Some signs of PJS can appear in childhood with the development of pigmented areas on the skin and in the mouth, called mucocutaneous hyperpigmentation. People with PJS tend to develop dark blue or dark brown freckling, especially around the mouth and on the lips, fingers, or toes. Freckles generally appear in childhood and often fade with age, so that they often are not visible in an adult with PJS newly diagnosed with cancer. Another sign of PJS is the development of hamartomatous polyps of the gastrointestinal tract that can cause bleeding and blockages. The average age when gastrointestinal symptoms appear is 10 years.

Individuals with at least 2 of the following characteristics may be considered to have PJS:

  • At least 2 Peutz-Jeghers type hamartomatous polyps in the small intestine

  • Characteristic freckling of the mouth, lips, fingers, or toes

  • At least 1 relative diagnosed with PJS

Individuals who meet these criteria are recommended to undergo genetic testing to look for an inherited mutation in the STK11 gene. More information is below.

What causes PJS?

PJS is a genetic condition that predisposes a person to an increased risk of developing cancer and polyps. This means that the condition can be passed from generation to generation in a family. PJS is caused by inheriting a mutation in the STK11 gene, also known as the LKB1 gene. It is possible that there are other genes that could cause PJS that have not yet been discovered

How is PJS inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. PJS is inherited in an autosomal dominant manner from a parent who carries the STK11 mutation. Each first-degree relative (a parent, child, and/or sibling) of an individual with PJS has a 50% chance that he or she has inherited the same mutation that causes this disease.

Some individuals with PJS have no family history of PJS or PJS-like symptoms or cancers. It is estimated that approximately 25% of individuals with PJS have a new (de novo) STK11 gene mutation that was not inherited from their parents. Family members of someone with a suspected de novo STK11 mutation should still undergo genetic testing to confirm that this was indeed a new mutation. A person who has a de novo STK11 mutation has a 50% chance of passing this mutation on to each of their biological children.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to have children who do not carry the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. The parents can then choose to transfer embryos that do not have the mutation. PGD has been in use for over 2 decades, and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

How common is PJS?

PJS is considered to be rare. It is estimated that between 1 in 50,000 to 1 in 200,000 people will have PJS. The syndrome may be underdiagnosed because the skin features like freckles or pigmented spots are often not visible in adulthood.

How is PJS diagnosed?

The diagnosis of PJS is assumed if someone meets the diagnostic criteria listed above. People who may possibly have PJS can have genetic counseling followed by genetic testing that includes a blood test to look for a mutation in the STK11 gene. If an STK11 gene mutation is found, other family members may also be diagnosed with PJS if they are tested and have the same gene mutation. However, some people with a clinical diagnosis of PJS will not have a detectable mutation in STK11. It is recommended that individuals with known or suspected PJS be evaluated by a specialist to confirm the diagnosis and assist with appropriate management.

What are the estimated cancer risks associated with PJS, by each type?

30% to 50%

40%

10% to 35%

30%

20%

15%

13%

10%

less than 10%

less than 10%

2%

What are the screening options for PJS or people at risk for PJS?

It is important to discuss with your doctor the following screening options, as each individual is different:

General cancer screening for anyone with PJS

  • Upper endoscopy and video capsule endoscopy, beginning at age 8. If polyps are seen, this should be repeated every 2 to 3 years. If no polyps are seen at age 8, these should be repeated by age 18, and then every 2 to 3 years afterwards. An endoscopy uses a thin, lighted, flexible tube with a small video camera that is inserted into your mouth and down your esophagus to look for tumors or other problems.

  • Colonoscopy, beginning at age 8. If polyps are seen, this should be repeated every 2 to 3 years. If no polyps are seen at age 8, this should be repeated by age 18, and then every 2 to 3 years afterwards. During a colonoscopy, doctor inserts a thin flexible tube with a small video camera into the anus to check for problems within the colon and rectum.

  • Endoscopic ultrasound and/or pancreatic MRI to screen for pancreatic cancer, beginning at age 30 and repeated every 1 to 2 years

  • Specific lung cancer screening is not currently recommended, but individuals with PJS should avoid smoking, due to the link with both lung and pancreatic cancers.

Cancer screening for women with PJS

  • Monthly breast self-examination and yearly clinical breast examination performed by a doctor or nurse, beginning at age 20

  • Mammogram every 2 to 3 years, beginning at age 20, and then a yearly mammogram, beginning at age 40

  • Yearly gynecologic examination including a Pap test, transvaginal ultrasound, and consideration of a uterine biopsy, beginning at age 25

  • Females with PJS are at risk for sex cord tumors with annular tubules (SCTAT), a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rare aggressive cancer often characterized by a heavy mucous-like vaginal discharge.

Cancer screening for men with PJS

  • Yearly testicular examination beginning in childhood. Testicular ultrasound should be performed to look for anything abnormal, or to investigate any signs of possible hormone problems.

  • Males may develop large calcium containing Sertoli cell tumors (LCST) of the testicles, which secrete estrogen and can lead to enlarged breasts (gynecomastia), advanced skeletal age, and ultimately short stature, if untreated.

Screening options may change over time as new technologies are developed and more is learned about PJS.  It is important to talk with your doctor about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans.

Questions to ask the doctor

If you are concerned about PJS and your risk of cancer, talk with your doctor. Consider asking the following questions of your doctor:

  • What is my risk of developing colorectal cancer, breast cancer, or other types of cancer?

  • How many colon polyps have I had in total?

  • What type of colon polyps have I had? The 2 most common kinds are hyperplastic and adenomatous.

  • What can I do to reduce my risk of cancer?

  • What are my options for getting a cancer risk assessment, genetic counseling, and possible genetic testing?

  • What are my options for cancer screening and prevention?

If you are concerned about your family history and think your family may have PJS, consider asking the following questions:

  • Does my family history increase my risk of colorectal cancer, breast cancer, or other types of cancer?

  • Does it suggest the need for a cancer risk assessment?

  • Will you refer me to a genetic counselor or other genetics specialist?

  • Should I consider genetic testing?

More Information

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet With a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

Additional Resources

Facing Our Risk of Cancer Empowered (FORCE)
www.facingourrisk.org

Colon Cancer Alliance
www.ccalliance.org

Pancreatic Cancer Action Network
www.pancan.org

National Cancer Institute
www.cancer.gov

American Cancer Society
www.cancer.org

CancerCare
www.cancercare.org

To find a genetic counselor in your area, ask your doctor or visit these websites: 

National Society of Genetic Counselors                    
www.nsgc.org

National Cancer Institute: Cancer Genetics Services Directory
www.cancer.gov/cancertopics/genetics/directory