What is Peutz-Jeghers syndrome (PJS)?
A syndrome is a group of features that often occur together. Peutz-Jeghers syndrome (PJS) is a hereditary condition that makes some people more likely to develop a certain type of polyp (tumor-like growth of tissue) in their gastrointestinal tract (stomach and intestines). People with PJS are also more likely to develop certain types of cancer, including colorectal, breast, stomach, and pancreatic, and specific types of tumors in the ovaries, cervix, and testes. Lastly, people with PJS often have small, dark freckles on certain areas of the body, which may fade as a person gets older.
The gastrointestinal polyps that develop in someone that has PJS are called hamartomatous Peutz-Jeghers-type polyps. The polyps grow mostly in the small intestine, colon (large intestine), stomach, and other sites. They can sometimes cause gastrointestinal bleeding, obstruction, and abdominal pain.Back to top
How is PJS diagnosed?
A diagnosis of PJS is made based on polyps or cancers that you have had, your family history, and genetic test results. About 80% of people who are diagnosed with PJS will have mutations in the STK11 gene. These mutations can be found through genetic testing.Back to top
What does a positive STK11 test result mean?
A positive test result means that person has a disease-causing genetic mutation in the STK11 gene. This means that the person has PJS and is believed to have an increased risk for developing hamartomatous Peutz-Jeghers-type polyps and certain cancers.
It is important to understand that having PJS does not mean that someone will definitely develop cancer; it just means that they have an increased risk of developing certain cancers. Some people with an STK11 mutation may never develop cancer.Back to top
What does a “variant of uncertain significance” (or “ambiguous”) genetic test result mean?
Genes are written in letters called bases. We call the wrong spelling of a gene a “mutation” and a mutation can cause an increased risk of cancer. However, some spelling changes in genes do not cause disease. We are still learning which spellings are normal (harmless) and which may cause disease. Some individuals’ STK11 gene may be spelled in a way that we cannot say whether it is normal or if it causes disease. These kinds of uncertain changes are called variants of uncertain significance.
If you have a variant of uncertain significance in the STK11 gene, we may not be able to tell you if it is a normal change or a disease-causing change. In some situations, we may be able to test your relatives for the variant or we may be able to do lab tests, but we still may not be able to tell if the variant will increase your risk for developing polyps or cancer. If you have a variant, we will make recommendations for cancer screening based on your family history.Back to top
What does a negative STK11 test result mean?
A negative test result means that no mutation was found in the STK11 gene. This could happen if:
- You have a mutation in the STK11 gene that cannot be detected with the testing method that was used. No one genetic testing method can find all mutations.
- You have a mutation in a different gene. Your genetic counselor may recommend testing for mutations in other genes that are also associated with hamartomatous polyps and certain cancers.
- Your personal or family history of PJS-like features could be related to other factors, such as age, environment, and chance.
- There is a genetic mutation in your family, but you did not inherit it.
How should people with PJS manage their risks for related cancers?
People with PJS have several options for managing their cancer risks. They can choose to undergo additional cancer screening or risk-reducing surgeries. The goal of screening is to detect cancer at an early stage. Screening for PJS includes the following:
- From birth, everyone should have a yearly physical exam with routine blood tests. Male children should also have a physical exam of the testicles, with optional testicular ultrasounds every 2 years.
- Starting at age 8, children should have an upper endoscopy and small bowel visualization. If polyps are found, these procedures should be repeated every 2 to 3 years.
- Adults should have a colonoscopy every 2 to 3 years starting at age 18. Starting at age 50, colonoscopies should be done yearly.
- Women should start monthly self-breast exams at age 18. At age 25, women should begin having breast exams done by a doctor or nurse twice a year, a yearly mammogram, and yearly breast magnetic resonance imaging (MRI) to screen for breast cancer. It is important to know that the risk-benefit ratio of mammography in very young women (under age 30) is under study.
- Women should have a pelvic exam and Pap smear every year beginning at age 21. Yearly transvaginal ultrasounds and a blood test called CA-125 may be done to screen for ovarian and uterine cancers beginning between the ages of 20 to 25; however, screening for gynecological cancers has not been proven to find cancer at an early stage or to lower the chance of dying from cancer. The risks and benefits of screening for these cancers should be discussed with a doctor who has knowledge about PJS.
- Men and women may consider pancreatic cancer screening every 1 to 2 years starting between the ages of 25 to 30. It is important to note though that there is no proven method of screening for pancreatic cancer. Some investigators are evaluating the role of periodic endoscopic ultrasound or MRI cholangiopancreatography (MRCP), but the benefits of these interventions are not defined.
It is important to realize that screening does not prevent cancer. Current tests cannot always find cancers when they are early enough to be treated successfully.
Preventative surgery should be considered for people who have:
- Many polyps that cannot be managed by endoscopy
- Precancerous polyps
- Troublesome diarrhea and bleeding
- Significant family history of colorectal cancer
Although surgery for cancer prevention has not been studied in people with PJS, women with an STK11 mutation may consider undergoing surgery to try to prevent certain cancers, such as breast and ovarian.Back to top
If I have an STK11 mutation, what are the risks to my children?
If you have an STK11 mutation, each of your children (or future children) has a 50% (1 in 2) chance of inheriting the mutation. A child who inherits the mutation will also inherit the associated risks. It is important to remember that inheriting the mutation does not mean that a person will definitely develop all features of PJS.
You may want to consider genetic testing in children who are at risk of having an STK11 mutation because there are certain cancer screenings they could do. Your genetic counselor can help determine the risk for your children and other family members, and will also determine what would be an appropriate age for them to undergo genetic testing.Back to top
If I have an STK11 mutation, what are my options for having children?
If you have an STK11 mutation, you may want to learn about family planning options (starting a family or having more children). For example, embryos can be tested for the family’s genetic mutation before they are even implanted in a woman’s uterus. This process is called preimplantation genetic diagnosis (PGD). PGD is performed with in vitro fertilization (IVF), and may be an option for families who wish to have children without the mutation. To learn more, ask for a referral to a PGD-IVF specialist before attempting pregnancy.
Other possible family planning options include having children with the assistance of donor eggs or donor sperm or through adoption.Back to top
What if I have questions?
If you have any questions or concerns, please contact the MSK Clinical Genetics Service at 646- 888-4050.Back to top