Peutz-Jeghers syndrome

Blood relatives of a person with Peutz-Jeghers syndrome (PJS) are all at risk to also have PJS. All first-degree relatives (parents, children, brothers, and sisters) of a person with a genetic mutation in the STK11 gene have a 50% risk to also have the mutation and have PJS. These individuals should consider being tested to see if they also carry the mutation. Early diagnosis can help reduce the chances of serious complications from the condition.

Consultation with a medical geneticist or genetic counselor is recommended before genetic testing so that all of the options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed.
Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in your area.

Rare diseases that affect multiple organ systems like Peutx-Jeghers syndrome (PJS) can benefit from a multidisciplinary approach. This approach involves healthcare professionals with specialized skills and expertise. They work together to make monitoring and treatment recommendations and to provide quality care of individuals and families. Depending upon the specific symptoms in an individual multidisciplinary team may require a specialist in cancer (oncologist); an gastrointestinal specialist (gastroenterologist); endocrinologist; a genetic counselor who can help people understand the disease and the implications for the person and other family members.

Talk to your doctor about the best specialists in your area to follow an individual with PJS syndrome.Your primary care physician or other health care provider can help refer you to PJS specialists in your area. You can also find a genetic counselor through the National Society of Genetic Counselors These specialists can help refer you to any other health care services you may need as part of your diagnosis and treatment.

There are several ways to connect with other people with Peutz-Jeghers syndrome, including online community forums such as Smart Patients. Your genetic counselor or medical genetics specialist can also help connect you to other families with Peutz-Jeghers syndrome.

Most people start getting screened for polyps as soon as symptoms start, and repeat them throughout their lifetime as recommended by their doctor. Children as young as eight years old may also begin to have these exams if they are found to be carriers of a STK11 mutation or have a high risk based on their family history.
People with PJS should also have a consultation with a genetic counselor to help understand the condition. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in your area.

Tests to see if there are growths in the GI tract include upper endoscopy and colonoscopy, where a flexible tube with a camera attached is inserted from the mouth down through the stomach and upper intestinal area (endoscopy) or inserted through the anus into the colon and large intestine (colonoscopy). Magnetic Resonance Imaging (MRI) may also be used to see growths in the intestines or in other parts of the body. Physical and visual examination of the skin and other parts of the body may also be performed.

The most common type of polyps in Peutz-Jeghers syndrome (PJS) are hamartomatous polyps. Hamartomatous polyps may be found in other cancer syndromes, but are commonly found in those affected by PJS.

Since Peutz-Jeghers is a genetic condition, people will usually see a doctor specializing in genetics (medical geneticist) or a genetic counselor at some point. If a person already has symptoms, such as growths of tissue (polyps) in the intestines, they may see several doctors to treat and manage the symptoms, such as a doctor specializing in the intestines (a gastroenterologist), a surgeon, and a doctor specializing in cancer (oncologist). If the person has other symptoms, they may also see other types of doctors.

There are also several different conditions that have symptoms similar to Peutz-Jeghers syndrome (PJS) so it is important to see a doctor specializing in genetics (medical geneticist) or a genetic counselor if you or your doctor thinks you have PJS. You can also find a doctor specializing in medical genetics through the American College of Medical Genetics and Genomics search page and a genetic counselor through the National Society of Genetic Counselors search page. These specialists can help confirm whether you have PJS and help you get the services you need for treatment if needed.

Hamartomatous polyps are the most common type of polyp in Peutz-Jeghers syndrome. A hamartomatous polyp is a type of abnormal cell growth that looks like a branching tree. These polyps can cause bowel blockage, rectal prolapse, and bleeding, and require surgery to remove. Other types of polyps are also seen, but are much less common.

Peutz-Jeghers-type hamartomatous polyps can occur anywhere in the GI tract, but occur most commonly in the small intestine. Polyps can also occur in the stomach and large bowel.

People with Peutz-Jeghers syndrome may have a shortened life span, primarily due to the high risks of cancer. Survival is dependent on the specific cancer diagnosis and prognosis. Early detection and treatment may increase survival rates. In addition, a healthy diet, exercise, avoidance of tobacco, and reduction of alcohol consumption may reduce the overall risks of cancer.

The STK11 gene (also called LKB1) provides instructions for making an enzyme called serine/threonine kinase 11. This enzyme is a tumor suppressor, which means that it helps keep cells from growing and dividing too fast or in an uncontrolled way. When working properly, the STK11 gene makes a protein that helps regulate cell growth and the body’s metabolism (the ability to convert food to energy). Mutations in the STK11 gene result in proteins that are not able to properly regulate cell growth, which causes polyps (abnormal growths of tissue) in the intestines, spots of dark skin freckling (mucocutaneous pigmentation), and an increased chance to develop cancer.

Peutz-Jeghers syndrome (PJS) is a genetic disorder that causes abnormal growths of tissue called hamartomas in the intestines and spots of dark skin freckling (mucocutaneous pigmentation) around the mouth, eyes, nostrils, fingers as well as inside the mouth. People with Peutz-Jeghers syndrome are at increased risk for developing some types of cancer during their lifetimes. Cancers of the gastrointestinal tract, pancreas, cervix, ovary, and breast are among the most commonly reported tumors.

People with Peutz-Jeghers syndrome (PJS) may have symptoms of tissue growths (polyps) in the intestines as early as childhood and will need to start getting colonoscopies and upper endoscopies (where a flexible tube with a camera attached is inserted either through the colon or mouth to see the intestinal tract) to detect and remove the polyps. They are at high risk for several different types of cancers and will require examinations and screening throughout their lifetime to try to detect and treat the cancers early, such as physical exams and possibly imaging, such as MRI.

Genetic testing for Peutz-Jeghers syndrome (PJS) includes looking for changes in the sequence of the DNA, specifically in the STK11 gene. Changes that causes the STK11 gene to not work properly are called pathogenic variants or mutations.

If an individual with PJS or family member is found to have a pathogenic variant or mutation in the STK11 gene, this means the diagnosis of PJS is confirmed.
If an individual with a known pathogenic variant or mutation in the STK11 gene is found not to have that chance, it is very unlikely they have PJS.
However, about 5% of people who have all of the symptoms of PJS do not have a pathogenic variant or mutation in the STK11 gene and that does not take away the diagnosis of PJS from them. Those individuals are still treated medically as if they have PJS.
If an individual with no signs of PJS and no family history of PJS has genetic testing that finds no changes in a STK11 gene, this means it is unlikely that they have PJS.

Another type of DNA change that may be found in genetic testing is called a variant of uncertain significance (VUS). This means that there was a change in the DNA making up the STK11 gene, but it is uncertain whether or not this change has an impact on the way the gene works. If you are found to have a VUS, additional testing may be available to you and/or your family members to try to find out whether or not the change is actually impacting the gene.

Consultation with a medical geneticist or genetic counselor is recommended before genetic testing so that all of the options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed.
Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in your area.

When you meet with a medical geneticist and/or genetic counselor, they will first try to gather information about your symptoms by asking you questions and reviewing your medical records. They will also ask you questions about your family’s health history to see if it is possible that your symptoms are related to a condition running in your family. If they think you may have a genetic condition, such as Peutz-Jeghers syndrome, they will discuss options for genetic testing to confirm the diagnosis.

In the vast majority (more than 95%) of people with Peutz-Jeghers syndrome (PJS), the condition is caused by a disease causing change, or mutation, in a gene called STK11. Genes are sections of DNA that carry the instructions to make proteins, which are molecules that carry out specific jobs in the body. When there is a mutation in the instructions carried by a gene, the protein is not made properly and is unable to perform its job properly.

A clinical diagnosis of Peutz-Jeghers syndrome (PJS) means that a person has enough physical symptoms of PJS that they can be treated as if they have the condition, even if they have not had genetic testing. In 5% of people with a clinical diagnosis of PJS, their genetic testing will not find a disease-causing change. However, they are still considered to have PJS and should be managed the same way as a person with genetically-confirmed PJS.

According to one clinical guideline, the diagnosis of PJS is established in a person with one of the following:

There are typically no distinctive facial features in individuals with Peutz-Jeghers syndrome. People with Peutz-Jeghers syndrome (PJS) typically develop spots of dark skin freckling (mucocutaneous pigmentation) around the mouth, eyes, nostrils, fingers as well as inside the mouth in childhood, but these dark areas usually fade by the teenage years to early adulthood. Some boys with PJS who have a specific type of testicular tumor (Sertoli cell tumor) may have increased breast development (gynecomastia) and may be shorter than average due to abnormal hormone production.

Individuals with Peutz-Jeghers syndrome (PJS) are at increased risk for cancers of the colon, stomach, breast, ovaries, pancreas, small bowel, cervix, uterus, testes, and lung. The average age of cancer onset is around 30-50 years of age.Patients with Peutz-Jeghers syndrome have an estimated 15-fold increased risk of developing intestinal cancer compared to the general population.

People with Peutz-Jeghers syndrome (PJS) usually have a specific type of polyp (abnormal growth of tissue) called a "hamartomatous polyp" in their gastrointestinal (GI) tract. GI polyps are most commonly found in the small intestine, but may also be located in other parts of the GI tract and body such as the stomach and large intestines. Polyps may result in health issues such as rectal bleeding, nausea, vomiting, and intestinal blockage. People with PJS also have darkening of the skin called a "mucocutaneous macule" around the mucous membranes (mouth, eyes, nostrils, anus). These dark blue to dark brown spots usually show up in childhood and fade by the teenage years or early adulthood. Individuals with Peutz-Jeghers syndrome are at increased risk for a wide variety of cancers including: colorectal, gastric, pancreatic, breast, and ovarian. Men with Peutz-Jeghers syndrome may occasionally develop breast enlargement (gynecomastia) and early maturing bone (advanced skeletal age) due to testes tumors (called large calcifying Sertoli cell tumors) of the testes, which secrete estrogen.

Once a person gets a diagnosis of Peutz-Jeghers syndrome, the first step is to see if they have the physical symptoms that go along with the condition and how far the condition has progressed. This can include a physical exam by a doctor specializing in PJS, genetic conditions, or other conditions that affect the GI tract, and tests, including scopes to see if the person has any growths in the GI tract.

Testing for Peutz-Jeghers syndrome is not part of routine prenatal screening or testing. The symptoms of Peutz-Jeghers syndrome also would not show up on a prenatal ultrasound. However, prenatal testing for Peutz-Jeghers syndrome can be done on an unborn baby (fetus) if there is already a known mutation in a parent or sibling of the fetus through a specialized procedure to get a sample of the placenta (chorionic villus sampling, or "CVS") or amniotic fluid (amniocentesis). The risks and benefits of prenatal testing for Peutz-Jeghers syndrome should be discussed with a genetic counselor. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in your area.

Genetic analysis of the STK11 gene can be completed through several different types of test to confirm Peutz-Jeghers syndrome (PJS).

If there is a known gene mutation in a family, targeted testing, also known as single site testing, can be ordered. With targeted testing, the laboratory will only look for one specific genetic change instead of scanning the entire gene. This is generally the least expensive option offered by testing companies. In order to have targeted testing, the doctor must provide a copy of the patient’s relative’s positive genetic test result so the laboratory knows what genetic change to test.

There are also testing options when a gene mutation has not been identified in the family. Many laboratories offer complete analysis of the STK11 gene. This analysis involves sequencing and deletion/duplication analysis of the STK11 gene.

There are numerous genes beyond STK11 gene that can be associated with hereditary cancer. In some situations, testing for multiple genes may be more efficient and/or cost-effective. This type of testing is often referred to as multi-gene testing or panel testing. Cancer panels often include PJS, and other genes that are associated with hereditary cancer.

Consultation with a medical geneticist or genetic counselor is recommended before genetic testing so that all of the options and possible test results can be discussed ahead of time. This individual will also help explain the test results and coordinate any follow-up as needed.
Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in your area.

Information on clinical research opportunities is available through the National Institutes of Health (NIH) clinicaltrials.gov. As of November 28, 2019 there are 8 studies actively recruiting patients with Peutz-Jeghers syndrome, ranging from registries to studies of drug therapies to genetic testing to procedures for early cancer screening.

There is currently no way to prevent the growth of polyps in people with Peutz-Jeghers syndrome. Therefore, care focuses on early detection and removal of polyps before they grow large enough to cause obstruction of the intestines.

The main treatment for Peutz-Jeghers syndrome is to remove any intestinal polyps. Although most polyps do not become cancerous, they can cause damage to the GI tract as they grow. Regular monitoring of polyp growth by internal scopes is recommended.
Prevention of other complications, such as cancer, may include preventive surgery or medications. These options vary for each individual and should be discussed with the medical team on a case-by-case basis.
There is typically no treatment for mucocutaneous lesions since these are not cancerous and do not carry any health risks.

The diagnosis of Peutz-Jeghers syndrome is based on clinical findings. Identification of a genetic change in the STK11 gene by molecular genetic testing confirms the diagnosis and allows family members to have genetic testing as well. Rarely (less than 5%), people who have all of the signs and symptoms of PJS do not have a mutation in the STK11 gene. Although the genetic cause of their condition is not confirmed, they are still cared for medically as if they have PJS. Their family members should still have high risk screening and monitoring for cancer, but they are unable to have genetic testing for the mutation in the family.

Genetic testing for Peutz-Jeghers syndrome usually happens after a person develops symptoms and is seen by a medical professional. Symptoms can show up anytime between childhood and adulthood, so people can be tested at any point in their lifetime. Once a person is found to have a genetic mutation, family members can also be tested for the mutation to see if they also have Peutz-Jeghers syndrome. Family members of a person with a known genetic mutation can be tested even before they have symptoms. This includes children and unborn babies.

Random mutations may occur in the STK11 gene, meaning that you may not have inherited the mutation from either parent, but instead, a mutation randomly happened in your while your cells were dividing. This happens in some individuals affected by Peutz-Jeghers syndrome (PJS). Approximately 45% of people with PJS have no family history, so these may be the random mutations.

The amount of people living with Peutz-Jeghers syndrome is not known for certain, but studies have suggested that it affects around 1 in 25,000 to 1 in 280,000 individuals worldwide.

Peutz-Jeghers syndrome (PJS) is caused by a disease related change, or mutation, in a gene called STK11. Everybody has two copies of each gene in every cell of their body. One copy of each gene is passed down from each parent. If a parent carries a mutation in one copy of their gene, there is a 50/50 chance the mutation will be passed down to each of their children, and a 50/50 chance the normal copy of the gene will be passed down to each of their children. This is called autosomal dominant inheritance.

To have a clinical diagnosis of Peutz-Jeghers syndrome (PJS), a person must have at least one of the following:

Peutz-Jeghers syndrome can be confirmed by genetic testing. A genetic test looks for changes in your DNA that cause areas of your body to not work properly. A small tube of blood or a saliva sample is collected and sent to a specialized laboratory for testing.

Genetic testing for Peutz-Jeghers syndrome has to be ordered by a medical professional, such as a doctor or a genetic counselor, after a visit to the medical clinic. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in your area.

The highest cancer risk in people with Peutz-Jeghers syndrome (PJS) is for gastrointestinal cancer. Routine screening to detect pre-cancerous changes to gastrointestinal polyps and removing them before they become cancerous is the main strategy for reducing cancer risk in people with PJS. This can entail removal of individual polyps or even parts of the colon or small intestine if there are too many polyps to remove individually.

For women with Peutz-Jeghers syndrome (PJS), breast examinations and MRI beginning at 18 years of age are recommended for early detection of cancers. Although removal of the breasts (mastectomy) and ovaries (oophorectomy) have not been specifically studied in women with PJS, these options may be considered for risk reduction.

Individuals interested in participating in a clinical research study, can visit Clinicaltrials.gov to learn more about the process and what studies may be available. On each study specific page, information about how to contact the doctor running the study at a specific site should be available. These individuals can be contact to learn more about participating in the study.

Not everyone with Peutz-Jeghers syndrome (PJS) will get all of the cancers listed above, but many will have at least one cancer. Individuals with PJS can speak with a medical geneticist or genetic counselor to help better understand their cancer risks. There are specific recommended screening and treatment plans that doctors will implement as makes sense with an individual’s personal health history and family health history to help detect cancer in its early stages for treatment.

You can find a doctor specializing in medical genetics through the American College of Medical Genetics and Genomics search page and a genetic counselor through the National Society of Genetic Counselors search page.

Not everyone with Peutz-Jeghers syndrome (PJS) will get cancer, but many people will. On average, the lifetime risks for different types of cancer in PJS are as follows:

A specific type of testicular tumor (Sertoli cell tumor) may develop in boys around 6-9 years of age. This type of tumor has a very low risk of becoming cancerous, but does cause abnormal hormone production that can result in increased breast development and short stature in males.

Peutz-Jeghers syndrome (PJS) usually does not cause learning disabilities or developmental differences. Individuals with Peutz-Jeghers syndrome are expected to have normal intelligence.

It is unclear whether different types of mutations in the STK11 gene cause different risks in Peutz-Jeghers syndrome. Different types of mutations may include a change in the DNA that is like a typo, where one letter is substituted for another (missense mutation) or a change due to a missing portion of DNA (deletion). In one study, age of onset of GI symptoms was noted to be earlier in individuals with a deletion than those with missense mutations. In another study, cancer risks were not found to differ based on mutation type.

Peutz-Jeghers syndrome (PJS) does not specifically affect a person’s ability to have children, though they may experience difficulty due to secondary complications from gastrointestinal obstruction or the development of cancer.
Each child of a person with a mutation in the STK11 gene, which causes PJS, is at 50% risk to also have the mutation and have PJS.
Prenatal testing for Peutz-Jeghers syndrome can be done on an unborn baby (fetus) if there is already a known mutation in a parent or sibling of the fetus through a specialized procedure to get a sample of the placenta (chorionic villus sampling, or "CVS") or amniotic fluid (amniocentesis). Testing of an embryo as part of the IVF process may also be available.
The risks and benefits of prenatal testing for Peutz-Jeghers syndrome should be discussed with a genetic counselor. Visit the National Society of Genetic Counselors website to learn more about genetic counseling services and to find a genetic counselor in your area.

More than half of people with a STK11 mutation get it from a parent who also has the mutation. However, about 45% of people with a STK11 mutation do not have any family history of PJS, so it is possible that the mutation happened for the first time in that person. This is called a "de novo" mutation. Either way, the children of a person with a STK11 mutation still has a 50/50 chance of getting the parent’s mutation.

Gastrointestinal polyps can develop in people with Peutz-Jeghers syndrome (PJS) at any age, including children. Most people with PJS will have at least one procedure to remove polyps by the time they are 18 years old. Screening of children with PJS for polyps may be recommended beginning as young as 8 years of age.

Mucocutaneous macules usually show up in early childhood and may fade in the teenage years and adulthood. Since these dark spots do not cause any health problems, screening and treatment are not necessary.

There are no specific recommendations for prevention of other types of cancer in people with PJS. Some protocols have been suggested for monitoring stomach, small and large bowel, breasts, testicles, ovaries, uterus, and pancreas by various procedures as early as birth and as frequently as once a year. Successful cancer treatment relies on early detection. However, a healthy diet, exercise, avoidance of tobacco, and reduction of alcohol consumption may reduce your overall risks of cancer.

Males with Peutz-Jeghers syndrome may develop a specific type of testicular tumor called a Sertoli cell tumor in childhood. These tumors do not usually cause become cancerous, but they can cause abnormal breast growth (gynecomastia) and short stature because of abnormal hormone production. Treatment with hormone therapy may lessen these symptoms.

In women with Peutz-Jeghers syndrome, ovarian growths called sex cord tumors with annular tubules (SCTATs) may also be present. These growths are not typically cancerous, but they may cause irregular or heavy periods and early puberty.

There are several different conditions that have symptoms similar to Peutz-Jeghers syndrome (PJS). In all of these conditions, the person has abnormal growths (polyps) in their gastrointestinal tract, like with PJS. However, these conditions are caused by mutations in genes other than STK11, which is the only gene known to cause PJS. An evaluation by a medical geneticist or consultation with a genetic counselor may help determine if you have PJS or another condition. Examples of other polyposis syndromes include:

A few support groups for Peutz-Jeghers syndrome can be found such as:

Hereditary Colon Cancer Foundation
Website: https://www.hcctakesguts.org/

Peutz-Jeghers Syndrome Online Support Group

Additional support may be found at the Genetic and Rare Disease Information Center and National Organization for Rare Diseases both have links to support groups for Peutz-Jeghers syndrome.

As of November 28, 2019 there is one drug therapy under investigation through the National Institutes of Health: Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome (PJS) is seen worldwide. It is not a condition that is isolated to a specific group of people.

People with Peutz-Jeghers syndrome (PJS) are usually born with a change (mutation) in the STK11 gene in every cell of their body. This is called a germline mutation because it was present in the original egg or sperm cell that came from the person’s parent, and was then incorporated into every cell of the person’s body. The genetic mutation may be inherited from a parent or may be new in this person as the embryo forms.