Peutz-Jeghers syndrome (PJS)

ALSO KNOWN AS: PJS, polyps and spots syndrome

RELATED CONDITIONS: Unexplained hamartomatous mixed polyposis

DEFINITION: Peutz-Jeghers syndrome (PJS) is a rare disorder that causes the growth of multiple benign polyps in the stomach and small intestines. PJS is transmitted as a familial autosomal dominant syndrome. Polyps characteristic of the syndrome usually begin to develop during childhood or early adulthood, and they have even been found in newborns. The average age of diagnosis is about twenty-three years in men and twenty-six years in women. The polyps often cause such medical problems as recurrent bowel obstructions, chronic bleeding, and abdominal pain, and they tend to become cancerous over time. PJS has also been found to increase an affected person’s risk of developing other cancers throughout the body, including breast, ovarian, uterine, pancreatic, esophagus, small intestine, and lung cancer.

Risk factors: Peutz-Jeghers syndrome is genetically linked, meaning that it is associated with a defect or mutation in one or more genes. A person at increased risk of developing this disorder usually has family members with the disease. The risk factors for people who develop PJS without a familial link are unknown. In these cases, the disease appears to result from new mutations in the gene responsible for the disorder, so exposure to chemicals in the environment may also be a risk factor.

Etiology and the disease process: Peutz-Jeghers syndrome is caused by a mutation in a tumor suppressor gene. Normally, during conception, two copies of each gene are passed on to the child, one from the mother and one from the father. In PJS, one inherited copy of a gene called serine/threonine-protein kinase 11, or STK11, is defective and is present in all cells, disrupting the cells’ ability to control division. Most cases of PJS are transmitted in an autosomal dominant pattern; however, some cases occur in people with no family history of PJS. Approximately 20 to 25 cases of PJS have no family history, but genetic testing can confirm the diagnosis. These cases are thought to occur due to de novo mutations in the STK11 gene. Mutations in the STK11 greatly increase the risk of developing the polyps that characterize PJS.

Incidence: Peutz-Jeghers syndrome is considered a rare disorder; its estimated incidence rate is between 1 in 25,000 and 1 in 300,000 in North America and Western Europe.

Symptoms: Individuals with Peutz-Jeghers syndrome commonly develop small, dark brown spots that resemble freckles around the eyes, lips, and nostrils; inside the mouth; around the anus; and, frequently, on the hands and feet. They typically appear during infancy or early childhood and gradually fade as the person ages. Many symptoms depend on the location and extent of the polyps or cancer and can include abdominal cramps and pain, bloody urine and stools, anemia, and vomiting (possibly with blood). Gynecomastia, an abnormal enlargement of the breasts, typically precedes the development of testicular, ovarian, and uterine cancer. Other findings in a patient with PJS include ovarian cysts, benign ear tumors, rectal prolapse, intussusception (part of the bowel folds into itself), and bladder, ureteral, intestinal, bronchial, and nasal polyps.

Screening and diagnosis: Screening for Peutz-Jeghers syndrome includes a blood test to look for a mutation in the STK11 gene. It is not routinely performed unless PJS is suspected, or other family members have been diagnosed with the disorder. Genetic testing and counseling remain key in diagnosing PJS.

An accurate family history and extensive physical examination, including genetic testing, are essential for diagnosing PJS. The syndrome is suspected when someone has a family history of PJS and the characteristic spots that accompany the disorder. Diagnostic tests should include an X-ray of the abdomen, upper and lower gastrointestinal studies, stool samples for occult blood, mammography, testicular ultrasound, and colonoscopy or sigmoidoscopy.

Staging of PJS is based on the cancers that develop.

Treatment and therapy: Treatment of Peutz-Jeghers syndrome may include surgery to remove polyps that are causing chronic problems (polypectomy). Advancing endoscopic techniques, including small-bowel capsule endoscopy and balloon-assisted endoscopy, have allowed for a less invasive and more thorough investigation of the gastrointestinal tract. Although most cases of intussusception resolve spontaneously, surgery may be needed to decrease bowel loss caused by intussusception. Repeated surgery to remove part of the intestine often results in short-bowel syndrome. This condition develops after bowel surgery when there is not enough surface area in the bowel to absorb sufficient nutrients from food. If this occurs, special nutritional interventions are required.

The primary goal in treating PJS, however, is the early identification of malignancies. Regular physical examinations and screening tests should be scheduled at recommended intervals to monitor polyps and detect cancers. Surveillance programs typically recommend that colon and testicular cancer screenings start between ages eight and ten, and that screening for most other cancers starts by age twenty.

Other treatments are specific to any cancers that may be identified.

Prognosis, prevention, and outcomes: The incidence of cancer in people with Peutz-Jeghers syndrome is high; it is estimated the lifetime cancer risk ranges from 37 percent to 93 percent. The average age of cancer diagnosis in a patient with PJS is forty-two. Intestinal, , pancreatic, breast, lung, uterus, ovary, cervix, and stomach cancers are among the most common. Forty percent of PJS patients develop colorectal cancer, and between 30 and 50 percent develop breast cancer. Death can occur as a result of complications of polyps, repeated surgeries, or cancer. There is no known method of preventing PJS.

Bibliography

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Van Lier, M. G. F., et al. "High Cancer Risk in Peutz-Jeghers Syndrome: A Systematic Review and Surveillance Recommendations." American Journal of Gastroenterology, vol. 105, 2010, pp. 1258–68.