Peutz-Jeghers syndrome

Alternate names

Polyposis, hamartomatous intestinal; PJS; Polyps-and-spots syndrome; Peutz Jeghers polyposis; Periorificial lentiginosis syndrome; Lentiginosis, perioral

Definition

Peutz-Jeghers syndrome is characterized by the development of noncancerous growths called hamartomatous polyps in the gastrointestinal tract (particularly the stomach and intestines) and a greatly increased risk of developing certain types of cancer.

Summary

People with Peutz-Jeghers syndrome have a high risk of developing cancer during their lifetimes. Cancers of the gastrointestinal tract, pancreas, cervix, ovary, and breast are among the most commonly reported tumors.

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Epidemiology

The prevalence of this condition is uncertain; estimates range from 1 in 25,000 to 300,000 individuals.

Cause

• Mutations in the STK11 gene (also known as LKB1) cause most cases of Peutz-Jeghers syndrome.
• The STK11 gene is a tumor suppressor gene, which means that it normally prevents cells from growing and dividing too rapidly or in an uncontrolled way.
• A mutation in this gene alters the structure or function of the STK11 protein, disrupting its ability to restrain cell division.
• The resulting uncontrolled cell growth leads to the formation of noncancerous polyps and cancerous tumors in people with Peutz-Jeghers syndrome.
• A small percentage of people with Peutz-Jeghers syndrome do not have mutations in the STK11 gene.
• In these cases, the cause of the disorder is unknown.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• Peutz-Jeghers syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing noncancerous polyps and cancerous tumors.
• In about half of all cases, an affected person inherits a mutation in the STK11 gene from one affected parent.
• The remaining cases occur in people with no history of Peutz-Jeghers syndrome in their family.
• These cases appear to result from new (de novo) mutations in the STK11 gene.

Signs and symptoms

• Peutz-Jeghers syndrome (PJS) is characterized primarily by an increased risk of growths along the lining of the gastrointestinal tract (called hamartomatous polyps) and certain types of cancer.
• Polyps are most commonly seen in the small intestines; however, they can also develop in the stomach, large intestines and other parts of the body such as the lungs, gall bladder, nose, and urinary bladder.
• Although these polyps are generally benign (noncancerous), they can be associated with many health problems including anemia, chronic bleeding, bowel obstruction, and intussusception.
• PJS-related polyps commonly present in adolescence or early adulthood with approximately a third of affected people experiencing symptoms in the first 10 years of life.
• Most affected people also have characteristic dark blue to dark brown macules around the mouth, eyes, and nostrils; near the anus (perianal); and on the inside of the cheeks (buccal mucosa).
• These spots may also occur on the hands and feet.
• They commonly appear during childhood and often fade as the person gets older.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal pigmentation of the oral mucosa
• Gastrointestinal carcinoma
• Multiple lentigines

30%-79% of people have these symptoms

• Gastrointestinal hemorrhage(Gastrointestinal bleeding)

5%-29% of people have these symptoms

• Abdominal pain(Pain in stomach)
• Abnormality of the gallbladder
• Abnormality of the ureter
• Anemia(Low number of red blood cells or hemoglobin)
• Biliary tract neoplasm
• Breast carcinoma(Breast cancer)
• Cervix cancer
• Enlarged polycystic ovaries(Enlarged ovaries with cysts)
• Esophageal neoplasm(Esophageal tumor)
• Gastrointestinal infarctions(Death of digestive organ tissue due to poor blood supply)
• Intestinal obstruction(Bowel obstruction)
• Melanonychia
• Multiple renal cysts(Multiple kidney cysts)
• Nasal polyposis
• Neoplasm of the colon(Colon tumor)
• Neoplasm of the lung(Lung tumor)
• Neoplasm of the nose(Nasal tumor)
• Neoplasm of the rectum(Rectal tumor)
• Neoplasm of the small intestine(Small intestine tumor)
• Pancreatic adenocarcinoma
• Rectal prolapse(Rectum protrudes through anus)
• Renal cell carcinoma(Cancer starting in small tubes in kidneys)
• Stomach cancer
• Vomiting(Throwing up)

Diagnosis

• A diagnosis of Peutz-Jeghers syndrome (PJS) is based on the presence of characteristic signs and symptoms.
• In people with a clinical diagnosis of PJS, genetic testing of the STK11 gene confirms the diagnosis in approximately 100% of people who have a positive family history and approximately 90% of people who have no family history of PJS.

Treatment

Polyps. Once the burden of gastrointestinal polyps has been established by endoscopy and imaging studies, prophylactic polypectomy of polyps >1cm is performed. This strategy has two goals:

• To decrease the sequelae of large polyps including bleeding, anemia, obstruction, and intussusception
• To reduce the risk for cancer by the malignant transformation of PJS-type polyps.

Distal small-bowel polyps that are beyond the reach of conventional endoscopy have been difficult to manage. Until recently, barium contrast upper-gastrointestinal series with a small-bowel follow through has been recommended. However, recent advances allow better diagnosis and eradication of small-bowel polyps, oftentimes without laparotomy and with a decrease in the radiation burden related to frequent surveillance:

Video capsule endoscopy (VCE) allows for better visualization of the small-bowel polyps than barium x-rays and is recommended as a first-line surveillance procedure. In children, the capsule can be deployed in the duodenum after upper endoscopy.

Magnetic resonance enterography (MRE) is a reliable procedure for the detection of larger small-bowel polyps with similar sensitivity to VCE and avoids the radiation exposure of CT enterography . CT and MR enteroclysis are alternative procedures but are less well tolerated.

Balloon-assisted enteroscopy can remove distal small-bowel polyps with or without laparotomy . Safety in those with PJS has been demonstrated in a few studies. Balloon-assisted enteroscopy and polypectomy should decrease the need for intraoperative enteroscopy or enterotomy, and should be reserved for affected individuals with many large and distal small-bowel polyps.

NIH genetic and rare disease info

• NIH info on Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is a rare disease.

Peutz-Jeghers syndrome Resources
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