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Peutz Jeghers syndrome

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Related Terms
  • Cancer of the gastrointestinal tract, gastrointestinal polyps, GI polyps, gynecomastia, hamartomas, hereditary intestinal polyposis syndrome, Hutchinson Weber-Peutz syndrome, intestinal cancer, intestinal hamartomatous polyps in association with mucocutaneous melanocytic macules, intestinal lesions, intestinal polyposis-cutaneous pigmentation syndrome, intestinal polyps, mucocutaneous melanocytic macules, periorificial lentiginosis syndrome, Peutz-Jeghers polyposis, PJS, polyposis hamartomatous intestinal, polyposis intestinal II, polyps and spots syndrome, polyps-and-spots syndrome, serine/threonine kinase 11 gene, Sertoli cell tumors, STK11 gene mutation, STK11/LKB1 gene mutation, tumor suppressor gene.

Background
  • Peutz Jeghers syndrome (PJS) is a rare genetic condition marked by the development of multiple noncancerous polyps, or small growths, on the lining of the gastrointestinal tract. These polyps, called hamartomas, occur most frequently in the small intestine but are also found in the stomach and large intestine. Other symptoms of PJS include discoloration of the skin around the eyes, nose, mouth, anus, hands, and feet. People with PJS are at increased risk of developing intestinal and other cancers. The average age of diagnosis is 23 years. However, symptoms can be identified at birth.
  • It is believed that PJS is caused by mutations or defects in the serine/threonine kinase 11 gene (STK11 or STK11/LKB1), which plays a role in the suppression of tumor growth. The STK11 gene provides instructions for making the STK11 protein. The signaling pathway of the STK11 gene product has not yet been identified. Being a tumor suppressor gene means that the overexpression of STK11 may result in cell growth arrest. When the gene is mutated, the structure or function of the STK11 protein is altered or impaired. In some individuals with PJS, the STK11 gene is not mutated. In these individuals, the cause of the disease is unknown.
  • About half of PJS cases are inherited, or passed down among family members. In the other half, individuals have no family history of the disorder. These cases result from a spontaneous genetic mutation in the egg, sperm cells, or developing embryo.
  • The exact prevalence of PJS is unknown, but it is estimated to occur in about 1 in 25,000-300,000 births in the United States. The international prevalence of PJS (outside of the United States) is unknown. PJS does not appear to affect one sex or ethnicity more than another.
  • About half of those with PJS die of cancer-related complications by age 60. Other individuals with PJS may have a normal life expectancy. Given that PJS is a genetic disorder, there is no cure. Treatment aims to reduce symptoms and prevent complications.

Diagnosis
  • General: Peutz Jeghers syndrome (PJS) is a rare genetic condition marked by the development of multiple noncancerous polyps, or small growths, on the lining of the gastrointestinal tract. These polyps, called hamartomas, occur most frequently in the small intestine but are also found in the stomach and large intestine. Other symptoms of PJS include discoloration of the skin around the eyes, nose, mouth, anus, hands, and feet. People with PJS are at increased risk of developing intestinal and other cancers. The average age at diagnosis is about 23 years in males and about 26 years in females. Skin discoloration, which tends to develop in early childhood, may make earlier diagnosis of PJS possible. Signs and symptoms that may point to a diagnosis of PJS include a family history of the disorder, unexplained abdominal pain and unexplained gastrointestinal bleeding in young people, irregular menstruation in females, development of breast tissue in males, early puberty, and bowel obstruction. In addition, females should receive a thorough gynecological and breast exam, including mammography, as some studies link PJS and cancers of the breast, uterus, and ovaries, while males should undergo screening for testicular abnormalities.
  • Physical exam: Individuals suspected of having PJS should receive a thorough physical exam and provide a complete family history, including any history of cancer. Signs and symptoms that may point to a diagnosis of PJS include a family history of the disorder, unexplained abdominal pain and gastrointestinal bleeding in young people, irregular menstruation in females, development of breast tissue in males, early puberty, and bowel obstruction.
  • Dermatological exam: A dermatologist or skin specialist can evaluate the skin discolorations known as mucocutaneous melanocytic macules, which usually look like small, flat, brown or dark blue freckle-like growths in and around the mouth (i.e., the lips, gums, and hard palate), near the nostrils and eyes, around the anus, and on the hands and feet.
  • Blood tests: Samples of blood may be taken to measure hematocrit, the proportion of blood volume occupied by red blood cells and iron level. These values may be low if blood is being lost because of unexplained gastrointestinal bleeding, which has been known to occur in patients younger than 25 years of age, and which can cause anemia.
  • Fecal occult blood test: A fecal occult blood test (FOBT) may be done if gastrointestinal bleeding is suspected. This test analyzes a stool sample for the presence of blood because unexplained gastrointestinal bleeding has occurred in some patients younger than 25 years of age.
  • Carcinoembryonic antigen test: The carcinoembryonic antigen (CEA) test has been used by clinicians to detect and monitor the development of noncancerous growths due to their potential to become cancerous. This test measures blood levels of the CEA protein, which is normally produced during fetal development and is not generally present in the blood of healthy adults. Presence of CEA in the blood may indicate the presence and severity of certain cancers, changes in cancer following the use of medications or surgery, and the return of cancer.
  • Imaging studies: Upper and lower endoscopies, in which a scope is introduced via the mouth or anus to examine the inside of the gastrointestinal system, may also be performed to assess the presence and severity of polyps.
  • Genetic testing: If PJS is suspected, DNA sequencing may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the STK11 gene. If this defect is detected, a positive diagnosis is made.
  • Prenatal DNA testing: If there is a family history of PJS, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) may be able to diagnose PJS. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.
  • During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
  • During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the STK11 gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications
  • General: There is no cure for Peutz Jeghers syndrome (PJS). Instead, treatment aims to reduce symptoms and prevent complications. Patients with PJS should be regularly be seen by a pediatrician, dermatologist, gastroenterologist, oncologist, and various surgeons.
  • Anemia: Bleeding of gastrointestinal polyps may cause persistent bleeding and eventually lead to anemia, a blood disorder characterized by low levels of red blood cells.
  • Bowel obstruction: Almost half of those with PJS develop bowel obstruction caused by the polyps that result from the disorder. The severity of bowel obstruction may depend on the size and location of the polyps, and generally occurs in the small intestine.
  • Cancer: Individuals with PJS are about 15 times more likely than the general population to develop cancer during their lifetime. About half those with PJS develop cancer and die by age 60, and the cumulative risk of developing cancer is estimated to be 93% by 64 years of age. Cancers in PJS typically occur in the gastrointestinal tract (i.e., the stomach, colon, small intestine, and esophagus), breast, ovaries, lung, cervix, testes, and uterus.
  • Sertoli cell cancer in male patients with PJS may result in the production of estrogen, thus causing feminization. Symptoms associated with Sertoli cell cancer include prominent external genitalia, pubic hair growth, accelerated skeletal and muscle development, and mature masculine voice in prepubertal males. Males may also show feminizing characteristics such as gynecomastia (breast tissue formation) and breast tenderness. Loss of libido, erectile dysfunction, and infertility have all been reported.
  • Pain: About one-quarter of individuals with PJS have abdominal pain caused by gastrointestinal polyps.

Treatment
  • General: There is no cure for Peutz Jeghers syndrome (PJS). Instead, treatment aims to reduce symptoms and prevent complications. Depending on individual symptoms and complications, individuals with PJS should be regularly seen by a geneticist, gynecologist, oncologist, dermatologist, and gastroenterologist.
  • Cancer treatment: People with PJS who develop cancer should receive standard cancer treatment. This often includes radiation and chemotherapy. By damaging the deoxyribonucleic acid (DNA) in the target cells, radiation therapy stops the growth of cancerous cells. While both normal and cancer cells are damaged by radiation, normal cells can typically recover, while cancer cells cannot. The goal of radiation therapy is to maximize damage to cancer cells and minimize damage to normal cells. About half of those with cancer receive radiation therapy in some form. Side effects of radiation therapy depend on the site of the radiation target and the type of cancer. For example, nausea, vomiting, and diarrhea may result from radiation therapy targeted at the stomach and related areas. Radiation may be used alone or in combination with other therapies, such as chemotherapy, which involves the use of drugs to stop cancerous cell growth. Again, however, chemotherapy can damage normal cells as well as cancerous cells. Side effects of chemotherapy may include nausea, vomiting, fatigue, pain, and loss of hair on the head and body.
  • Iron supplementation: Iron supplementation may be prescribed to individuals who develop iron deficiency anemia, a blood disorder characterized by low levels of red blood cells.
  • Surgery: Surgical removal of large polyps may be appropriate to reduce pain, bleeding, and risk of bowel obstruction. Surgery is also an option for the removal of cancerous growths.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. American Cancer Society, Inc. .
  2. Boardman LA, Thibodeau SN, Schaid DJ. Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med. 1998;128(11):896-9.
  3. Georgescu EF, Stanescu L, Simionescu C, et al. Peutz-Jeghers syndrome: case report and literature review. Rom J Morphol Embryol. 2008;49(2):241-5.
  4. Giardiello FM, Brensinger JD, Tersmette AC. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 2000;119(6):1447-53.
  5. Jenne DE, Reimann H, Nezu J. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18(1):38-43.
  6. Natural Standard: The Authority on Integrative Medicine. .
  7. Peutz-Jeghers syndrome. .
  8. Rebsdorf Pedersen I, Hartvigsen A, Fischer Hansen B. Management of Peutz-Jeghers syndrome. Experience with patients from the Danish Polyposis Register. Int J Colorectal Dis. 1994;9(4):177-9.
  9. Westerman AM, Entius MM, de Baar E. Peutz-Jeghers syndrome: 78-year follow-up of the original family. Lancet. 1999;353(9160):1211-5.

Causes
  • Genetic mutations: Peutz Jeghers syndrome (PJS) is usually caused by mutations or defects in the serine/threonine kinase 11 gene (STK11 or STK11/LKB1), which provides instructions for making the STK11 protein. The STK11 gene plays a role in the suppression of tumor growth. When the gene is mutated, the structure or function of the STK11 protein is altered, which changes its ability to regulate cell growth, possibly resulting in tumor formation.
  • Some researchers suggest that an additional genetic mutation may play a role in the development and progression of PJS. Whether this mutation occurs in the other STK11 gene or in a different gene altogether is currently unknown.
  • How these genetic mutations lead to the formation of hamartomatous polyps, which are noncancerous growths that occur in the intestines, and the characteristic skin discoloration found in PJS patients is not well understood. In some individuals with PJS, the STK11 gene is not mutated. In these individuals, the cause of the disease is unknown.
  • Autosomal dominant inheritance: About half of PJS cases are inherited, or passed down among family members, as an autosomal dominant trait. People inherit two copies of most genes, one from the mother and one from the father. To inherit an autosomal dominant trait, an individual needs to inherit only one defective copy of the causative gene. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder. (By contrast, to inherit an autosomal recessive trait, an individual must inherit two defective copies of the causative gene.)
  • Random occurrence: The other half of PJS cases occur in individuals with no family history of the disorder. These cases result from a spontaneous genetic mutation in the egg, sperm cells, or developing embryo.

Risk factors
  • Peutz Jeghers syndrome (PJS) may be an inherited condition; therefore, a risk factor is a family history of the disease.
  • About half of PJS cases are inherited, or passed down among family members, as autosomal dominant traits. People inherit two copies of most genes, one from the mother and one from the father. To inherit an autosomal dominant trait, an individual needs to inherit only one defective copy of the causative gene. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder.
  • The other half of PJS cases occur in individuals with no family history of the disorder. These cases result from a spontaneous genetic mutation in the egg, sperm cells, or developing embryo. There are no known risk factors for this method of occurrence.
  • The exact prevalence of PJS is unknown, but it is estimated to occur in about 1 in 25,000-300,000 births in the United States. The international prevalence of PJS (outside of the United States) is unknown. PJS does not appear to affect one sex or ethnicity more than another.

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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.