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:
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 is believed that through a combination of these mechanisms, STK11 aids in the prevention of tumors.
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 altered so that it does not function properly. Patients are born and develop normally, but are at an increased risk to develop non-cancerous and cancerous growths. These growths are believed to develop because, over time, the second working copy of the STK11 gene may become altered 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 an alteration in one copy of the STK11 gene has a 50 percent (or 1 in 2) chance of passing this same alteration on to each of his or her children. Children who inherit the altered gene copy will have Peutz-Jeghers syndrome and will therefore be at increased risk to develop 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 offspring will now 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 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 10 years of age, and children most often had their first polyps removal (polypectomy) at 13 years of age (Amos et al., 2004).
Mucocutaneous pigmentation (altered coloring of the skin, gums and other mucus membranes) is rarely present at birth, but develops during early childhood (usually before 5 years of age) as dark blue to dark brown flat spots in the following areas:
The spots can fade in puberty and adulthood. One report estimates that 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.
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 that 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.
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 that genetic testing be performed.
In order to confirm on a molecular level that an individual has Peutz-Jeghers syndrome, he or she can undergo the process of genetic testing:
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, it is important to remember that 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 exist for an individual with an alteration in the STK11 gene who does not wish to pass this alteration on to future children:
Before one can proceed with prenatal testing or PGD, a STK11 mutation must be identified in a parent with PJS.
Individuals carrying an alteration in one copy of the STK11 gene are born and develop normally, but they are at an increased risk to develop a variety of cancers, including:
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 years. In women with Peutz-Jeghers syndrome, the risk of breast cancer was estimated to be 8 percent and 31 percent at ages 40 and 60 years, respectively.
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:
Pancreatic cancer screening:
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.
Gynecologic (ovary and uterus):
Currently, there are no guidelines regarding surveillance for development of lung cancer in people with Peutz-Jeghers syndrome.
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:
Patients and parents should be alert to signs and symptoms of illness and pursue medical attention promptly should these occur.
We recommend that children with a diagnosis of Peutz-Jeghers syndrome, or those suspected of having Peutz-Jeghers syndrome, contact the Division of Gastroenterology, Hepatology and Nutrition at The Children's Hospital of Philadelphia to discuss issues related to the management of this condition. Please call 215-590-3630 to schedule an appointment.
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 by calling the coordinator, Samantha Halter, at 215-898-0154 or firstname.lastname@example.org.
American Cancer Society (for information on regional support)
1599 Clifton Rd. NE
Atlanta, GA 30329
Colon Cancer Alliance
1200 G Street, NW
Washington, DC 20005
Peutz-Jeghers Syndrome and Juvenile Polyposis Syndrome Online Support Group
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. Read the article
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. Read the article
Reviewed by: Kim Nichols, MD, Kristin Zelley, MS
Date: September 2012