Peutz-Jeghers Syndrome (PJS)

What is Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome (PJS) is a hereditary cancer syndrome identified by the presence of gastrointestinal polyps and altered pigmentation (freckling) of certain skin and mucosal areas. The polyps in individuals with PJS are most often found in the small intestine, but also occur in other parts of the gastrointestinal tract.

In addition to polyps, people with Peutz-Jeghers syndrome are at an increased risk for developing certain types of cancers:

  • Colorectal cancer
  • Gastric (stomach) cancer
  • Pancreatic cancer
  • Breast cancer
  • Uterine and cervical cancer
  • Lung cancer
  • Benign and malignant tumors of the ovaries and testicles

Because Peutz-Jeghers syndrome is hereditary, the risk of developing the features associated with PJS can be passed from generation to generation in a family.


Peutz-Jeghers syndrome is caused by alterations (mutations), at a specific area in a person’s genetic information. Each of us has a large amount of genetic information that is organized into smaller segments known as "genes." Genes provide the instructions that our cells need to perform different functions within our bodies.

There is a specific gene known as STK11 (also known as LKB1), located on chromosome 19 at position q13.3, that is altered in patients with Peutz-Jeghers syndrome. The STK11 gene has the ability to produce an enzyme called "serine/threonine kinase 11" that has several important functions:

  • It acts as a tumor suppressor — the enzyme keeps cells from growing and dividing too quickly and it promotes cell death.
  • It helps certain types of cells correctly orient themselves within tissues.  
  • It helps determine the amount of energy a cell uses.

It is believed that through a combination of these mechanisms, STK11 aids in the prevention of tumors.

How is Peutz-Jeghers syndrome (PJS) inherited?

With the exception of egg and sperm cells, each cell of the body normally has two working copies of the STK11 gene. In patients with Peutz-Jeghers syndrome, however, each cell contains only one working STK11 copy. While the second copy is present, it is mutated so it does not function properly.

Patients with PJS are born and develop normally, but are at an increased risk of developing non-cancerous and cancerous growths. These growths are believed to develop because, over time, the second working copy of the STK11 gene may become damaged within one or more cells. This can lead to abnormal proliferation of the affected cells, increasing their chance to form tumors or cancer.

A person carrying a mutation in one copy of the STK11 gene has a 50 percent — or one in two — chance of passing this same alteration onto each of his children. Children who inherit the altered gene copy will have Peutz-Jeghers syndrome and be at increased risk of developing cancer and other features associated with this condition.

Approximately 50 percent of patients with Peutz-Jeghers syndrome inherit an altered copy of the STK11 gene from a parent who also has PJS. In the remaining 50 percent of patients, there is no family history of Peutz-Jegher syndrome. In these individuals, PJS likely results from occurrence of a "new mutation" in one copy of the STK11 gene. Although these individuals will be the first ones in their family to carry the genetic change, each of their future children will have a 50 percent chance of inheriting the same genetic change.


The diagnosis of Peutz-Jeghers syndrome relies primarily on the presence of certain symptoms, including hamartomatous (benign, non-cancerous) intestinal polyps, altered pigmentation of the skin and mucus membranes, and/or a family history of PJS.

The symptoms of Peutz-Jeghers syndrome can vary within a family. Some affected individuals may have only polyps or altered pigmentation, while others may develop more extensive symptoms. Since people with PJS often show subtle symptoms, it is possible this condition is under-diagnosed in families and that more individuals with Peutz-Jeghers syndrome have inherited the condition from their parents than currently thought.

Intestinal polyps

The polyps seen in individuals with Peutz-Jeghers syndrome are most often found in the small intestine, but they can also occur in the stomach and large bowel. During childhood, polyps are typically non-cancerous, but they can bleed and cause anemia (lowering the level of healthy red blood cells) and block the intestines. The age at which polyps are first observed in individuals with PJS can vary among families. One study showed that children most often showed their first gastrointestinal symptoms at age 10 years, and children most often had their first polyps removal (polypectomy) at age 13 (Amos et al., 2004).

Mucocutaneous pigmentation

Mucocutaneous pigmentation (altered coloring of the skin, gums and other mucus membranes) is rarely present at birth, but develops during early childhood (usually before age 5) as dark blue to dark brown flat spots around the mouth, eyes and nostrils; in the peri-anal area; on the gums; and on the fingers. The spots can fade in puberty and adulthood. One report estimates 82 percent of patients with Peutz-Jeghers syndrome have freckling (Amos et al., 2004). That means approximately 18 percent of patients do not have freckling but remain at risk to develop other features of PJS.

Family history

A careful and detailed review of a person's medical and family history is important in diagnosing Peutz-Jeghers syndrome. A doctor or genetic counselor may construct a pedigree, or a multi-generation family tree, that shows which members of the family have developed cancer, the types of cancer and the ages of onset, as well as the presence of any symptoms. If the pattern of symptoms and/or cancers is suggestive of Peutz-Jeghers syndrome, the physician or counselor may recommend genetic testing be performed.

Testing for Peutz-Jeghers syndrome (PJS)

Genetic testing can confirm on a molecular level whether an individual has Peutz-Jeghers syndrome:

  • First, a blood or saliva sample is obtained.
  • DNA is isolated from the sample and the two copies of the STK11 gene are evaluated using a variety of methods and compared to the normal reference sequence for STK11.
  • If an alteration in one STK11 gene copy is identified, the genetic counselor can next examine whether the alteration has been previously reported in other individuals with Peutz-Jeghers syndrome.

This information could further strengthen the conclusion that the STK11 alteration was the cause of the symptoms in the individual.

In individuals with a clinical diagnosis of PJS, molecular genetic testing of the STK11 gene reveals disease-causing alterations in approximately 100 percent of individuals who have a positive family history. Approximately 90 percent of individuals who have a clinical diagnosis but no family history of Peutz-Jeghers syndrome are found to have an alteration in STK11. However, not all patients with Peutz-Jeghers syndrome carry a detectable alteration in the STK11 gene. Therefore, the failure to identify an alteration in the STK11 gene does not exclude a diagnosis of PJS.

STK11 genetic test results can also provide important information for other family members. Knowing the specific alteration that is present in a person with Peutz-Jeghers syndrome allows other family members to undergo testing to determine whether they also carry the alteration and could therefore develop the features of PJS.

Reproductive options

Reproductive options exist for an individual with an alteration in the STK11 gene who does not wish to pass this alteration onto future children:

  • Prenatal diagnosis — DNA is isolated from the cells of the developing baby though one of two procedures (chorionic villus sampling [CVS] or amniocentesis) and is analyzed for alterations in the STK11 gene. With appropriate counseling, a parent can then decide whether to carry the pregnancy to term or to end the pregnancy.
  • Preimplantation genetic diagnosis (PGD) — For couples using in vitro fertilization to become pregnant, embryos can be tested for genetic disorders before transferring them into the uterus. Only healthy embryos carrying two working copies of the STK11 gene would be implanted.

Before one can proceed with prenatal testing or PGD, a STK11 mutation must be identified in a parent with PJS.

Cancer risks

Individuals carrying an alteration in one copy of the STK11 gene are born and develop normally, but are at increased risk of developing a variety of cancers, including:

  • Colorectal cancer
  • Gastric cancer
  • Pancreatic cancer
  • Breast cancer
  • Ovarian cancer
  • Uterine cancer
  • Cervical cancer
  • Lung cancer
  • Certain benign and malignant gynecologic and gonadal tumors.

Among the various cancer types, gastrointestinal and breast cancers are by far the most frequent. The risk of gastrointestinal cancer is estimated to be 15 percent by age 50 and 57 percent by age 70. In women with Peutz-Jeghers syndrome, the risk of breast cancer was estimated to be 8 percent at age 40, and 31 percent at age 60.

Follow-up care

Cancer screening

Regardless of whether one decides to pursue testing for STK11 mutations, the following surveillance recommendations from the National Comprehensive Cancer Network (2012) are strongly recommended.

Stomach, small and large bowel cancer screening:

  • Upper endoscopy (a procedure that lets the doctor see the inside lining of the digestive tract) beginning in the late teenage years (for baseline screening) and repeated every 2-3 years into adulthood
  • Small bowel visualization beginning at age 8 to 10 (for baseline screening) with follow-up based on findings, but at least by age 18, then every 2-3 years or as recommended based on findings or symptoms
  • Colonoscopy beginning in the late teenage years and repeated every 2-3 years (or earlier if symptoms arise)

Pancreatic cancer screening:

  • Consider magnetic resonance cholangiopancreatography (MRCP) (MRI of the pancreatic and bile ducts) and/or endoscopic ultrasound (a procedure that combines endoscopy and ultrasound to obtain images and information about the digestive tract and the surrounding tissue and organs) beginning at age 25 to 30 and repeated every 1-2 years
  • Consider CA 19-9 levels performed at similar intervals.

It is important to note that pancreatic cancer screening should only be performed in a center with experience in managing pancreatic disease, and should involve a thorough discussion of the benefits, risks, and limitations of pancreatic cancer screening.

Cancer screening for women


  • Monthly breast self-examination and every 6 month clinical breast examination beginning at age 25 
  • Annual mammograms and breast MRIs beginning at age 25

Gynecologic (ovary and uterus):

  • Yearly gynecologic examination including Pap test
  • Consider yearly transvaginal ultrasound (a test where a small ultrasound probe is inserted like a speculum for a pelvic examination to obtain better imaging of the uterus) beginning at age 18 to 20

Cancer screening for men


  • Yearly testicular examination and observation for feminizing changes and consideration of ultrasound beginning by age 10

Lung cancer screening

Currently, there are no guidelines regarding surveillance for development of lung cancer in people with Peutz-Jeghers syndrome.

Healthy lifestyle

In addition to following recommended cancer surveillance guidelines, children and adults with Peutz-Jeghers syndrome should be encouraged to lead as healthy a lifestyle as possible, using these safeguards:

  • Avoid excess sun exposure
  • Use sunblock and a hat when out in the sun
  • Avoid tobacco use
  • Limit exposure to tobacco smoke

Patients and parents should be alert to signs and symptoms of illness and pursue medical attention promptly should these occur.

Clinical services


We recommend children with a diagnosis of Peutz-Jeghers syndrome, or those suspected of having Peutz-Jeghers syndrome, contact CHOP's Division of Gastroenterology, Hepatology and Nutrition.


Adults who have Peutz-Jeghers syndrome or who would like more information about Peutz-Jeghers syndrome may contact the Gastrointestinal (GI) Cancer Risk Evaluation Program at the Hospital of the University of Pennsylvania.


Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity TJ, Seldin MF, et al. Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet. 2004 May;41(5):327-33. Cited in PubMed; PMID 15121768.

Hearle N, Schumacher V, Menko FH, Olschwang S, Boardman LA, Gille JJ, et al. Frequency and spectrum of cancers in Peutz-Jeghers syndrome. Clin Cancer Res. 2006 May 15;12(10):3209-15. Cited in PubMed; PMID 16707622. 

Reviewed by Kristin Zelley, MS, LCGC

Providers Who Treat Peutz-Jeghers Syndrome (PJS)