Peutz-Jeghers syndrome (PJS) is a rare, inherited condition affecting approximately 1 in 25,000 to 300,000 live births. This disorder is characterized by distinctive dark spots on the skin and mucous membranes, alongside the growth of hamartomatous polyps, primarily within the gastrointestinal tract. While these polyps are initially benign, their presence indicates a higher risk for certain health concerns.
Symptoms and Physical Signs
Individuals with PJS often present with two main types of signs, typically appearing during childhood. Small, dark-colored spots, known as mucocutaneous hyperpigmentation, are a common manifestation. These blue-gray or brown spots, usually 1 to 5 millimeters in size, are most frequently observed around the mouth, on the lips, inside the cheeks, near the eyes and nostrils, and sometimes on the fingers and toes. While they often develop between ages 1 and 2, these spots may fade as individuals reach their late teens or adulthood, though they tend to persist inside the mouth.
The other primary set of symptoms arises from hamartomatous polyps that form in the gastrointestinal tract. These growths can cause various issues, including abdominal pain. Rectal bleeding from the polyps can occur, which may lead to iron-deficiency anemia. The polyps can also grow large enough to cause blockages in the intestines or lead to a condition where one part of the intestine telescopes into another, known as intussusception.
Genetic Cause and Inheritance
Peutz-Jeghers syndrome is primarily caused by a mutation in the STK11 gene, also known as LKB1. This gene normally functions as a tumor suppressor, helping regulate cell growth and division.
When a mutation occurs in STK11, this regulatory function is disrupted, which can lead to uncontrolled cell growth and the formation of polyps. PJS follows an autosomal dominant inheritance pattern, meaning that if one parent carries the mutated gene, each child has a 50% chance of inheriting the condition. While most cases are inherited, some individuals with PJS are the first in their family to have the condition due to a spontaneous mutation in the STK11 gene.
The Diagnostic Process
Diagnosing Peutz-Jeghers syndrome involves a combination of clinical observations and specific medical tests. Clinical criteria often include the presence of two or more PJS-type hamartomatous polyps in the gastrointestinal tract, or any number of such polyps combined with the characteristic mucocutaneous pigmentation. A family history of PJS, along with either polyps or skin spots, also supports a diagnosis. The distinctive dark spots around the mouth and on other areas can be an early indicator, especially in children.
To visualize and identify polyps, doctors use endoscopic procedures. An upper endoscopy allows examination of the esophagus, stomach, and the first part of the small intestine. A colonoscopy is performed to inspect the large intestine for polyps. For areas of the small intestine that are harder to reach, a video capsule endoscopy, where a small camera is swallowed, or an MRI enteroclysis may be used to capture images of the digestive lining. Genetic testing confirms the diagnosis by identifying a mutation in the STK11 gene.
Associated Health Risks
Individuals with Peutz-Jeghers syndrome face a significantly increased lifetime risk of developing various cancers. The overall lifetime cancer risk can be as high as 93%, with cancers often appearing at younger ages than in the general population. Gastrointestinal cancers are particularly common, including colorectal cancer (up to 40%), stomach cancer (up to 30%), and small intestine cancer (up to 13%). Pancreatic cancer risk is also elevated, ranging from 11% to 36% over a lifetime.
Beyond the digestive system, individuals with PJS have increased risks for other types of cancer. Women have a higher lifetime risk for breast cancer, which can be between 30% and 54%. There are also elevated risks for lung cancer (around 15-17%), ovarian cancer (18-21%), and cervical cancer (around 10%). PJS can also lead to serious non-cancerous complications. Intussusception, where a segment of the intestine folds into another, is a frequent and potentially life-threatening complication, occurring in up to 69% of individuals, often requiring emergency surgery. Polyps can also cause chronic gastrointestinal bleeding and intestinal obstruction.
Management and Surveillance
Management of Peutz-Jeghers syndrome primarily focuses on proactive surveillance to detect polyps and potential cancers early. Regular monitoring is implemented to address complications and improve outcomes. Endoscopic procedures are a key part of this management, with regular upper endoscopies and colonoscopies recommended. These procedures allow for the visualization and removal of polyps, a process called polypectomy, before they can cause symptoms like bleeding, obstruction, or intussusception. Polyps larger than 15-20 mm are targeted for removal to prevent such complications.
Surveillance protocols extend to screening for various cancers. For women, regular mammograms are advised to screen for breast cancer, often starting at an earlier age than in the general population. Imaging techniques like endoscopic ultrasound or MRI scans are used to monitor for pancreatic cancer, with recommendations for screening often beginning around age 30 or earlier if there is a family history of pancreatic cancer. While there is no treatment to stop the syndrome’s progression, these systematic screenings and interventions aim to reduce the risks associated with PJS.