Information for Health Professionals, Polyposis

Peutz-Jeghers Syndrome (PJS)


English: Structure of the LKB1 (pink)- STRAD (...

Structure of the LKB1 protein

Disease characteristics. Peutz-Jeghers syndrome(PJS (OMIM 175200)) is characterized by the association of gastrointestinal polyposis and mucocutaneous pigmentation.  Gastrointestinal cancer risks include gastro-oesophageal, small bowel, pancreatic and colorectal cancers with a cumulative risk of 57% by the age of 70.  here is a 50% lifetime risk of breast cancer, and clinicians managing PJS patients should ensure breast screening arrangements are in place. In 2063% of cases, inactivating mutations can be identified in the gene STK11 (LKB1). There is evidence for genetic heterogeneity with a possible further locus on chromosome 19q. Estimates of the population prevalence of PeutzJeghers syndrome suggest a frequency of around 1:50 000.

Peutz-Jeghers-type hamartomatous polyps are most common in the small intestine (in order of prevalence: in the jejunum, ileum, and duodenum) but can also occur in the stomach, large bowel, and nasal passages. Gastrointestinal polyps can result in chronic bleeding and anemia and cause recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection.

English: Low magnification micrograph of a Peu...

English: Low magnification micrograph of a Peutz-Jeghers type intestinal polyp. H&E stain. (Photo credit: Wikipedia)

Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are common. The macules may fade in puberty and adulthood. Individuals with Peutz-Jeghers syndrome are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers). Females are at risk for sex cord tumors with annular tubules (SCTAT), a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rare aggressive cancer. Males occasionally develop calcifying Sertoli cell tumors of the testes, which secrete estrogen and can lead to gynecomastia.

Diagnosis/testing. The diagnosis of Peutz-Jeghers syndrome is based on clinical findings. In individuals with a clinical diagnosis of PJS, molecular genetic testing of STK11 (LKB1) reveals disease-causing mutations in nearly all individuals who have a positive family history and approximately 90% of individuals who have no family history of PJS. Such testing is available clinically.

Management.

English: A graphical representation of the nat...

English: A graphical representation of the natural history of Peutz-Jeghers syndrome. Most patients will develop melanotic macules during the first year of life and a patient’s first intussusception usually occurs between the ages of six and 18 years old. Cumulative lifetime cancer risk begins to rise in middle age. Cumulative risks by age 70 for all cancers, gastrointestinal (GI) cancers, and pancreatic cancer are 85%, 57%, and 11%, respectively. (Photo credit: Wikipedia)

Colorectal surveillance

Large bowel surveillance is recommended 2-yearly from age 25 years. The intervention should visualise the whole colon and so colonoscopy is the preferred mode of surveillance. PJS is rare and so evidence on effectiveness of surveillance is limited to case series and anecdote.  The risk of colorectal cancer increases with age being 3%, 5%, 15%, and 39% at ages 40, 50, 60, and 70 years, respectively. Males may be at greater risk. There is also an excess risk of small bowel, pancreatic and oesophago-gastric cancer. The risk for all gastrointestinal cancers combined is 1%, 9%, 15%, 33%, and 57% up to ages 30, 40, 50, 60 and 70 years, respectively.154

Treatment of other manifestations:

Upper gastrointestinal surveillance is recommended 2-yearly from age 25 years, comprising gastro-duodenoscopy. Intermittent MRI enteroclysis or small bowel contrast radiography is recommended.

There is an elevated risk of gastric malignancy in PeutzJeghers syndrome amounting to around 510%.  Although evidence from pooled case series indicates that small intestinal cancer is rare, the risk is sufficient to merit intermittent imaging.  MRI enteroclysis appears appropriate for surveillance because it avoids repeated radiation exposure in young individuals and has very good sensitivity and overall accuracy for small bowel polyps in PJS as well as for patients with small bowel tumours who do not have PJS.  However, video capsule endoscopy is also an option, with evidence of better sensitivity than MRI enteroclysis for smaller lesions in small bowel polyposis syndromes in one small comparative study.

Testing of relatives at risk: If the family mutation is known, offer molecular genetic testing to at-risk relatives so that morbidity and mortality can be reduced in those with the family-specific mutation by early diagnosis and treatment and appropriate surveillance; if the family mutation is not known, offer clinical diagnostic evaluations to identify those family members who will benefit from early treatment and appropriate surveillance.

Other: Although not studied in individuals with PJS, the following could be considered: prophylactic mastectomy to manage high risk for breast cancer and prophylactic hysterectomy and bilateral salpingo-oophorectomy after age 35 years or after child-bearing has been completed to prevent gynecologic malignancy.

Genetic counseling. Peutz-Jeghers syndrome is inherited in an autosomal dominant manner. About 50% of affected individuals have an affected parent and about 50% have no family history of PJS; the proportion of cases caused by de novo gene mutations is unknown as the frequency of subtle signs of the disorder in parents has not been thoroughly evaluated and molecular genetic data are insufficient. The risk to the offspring of an individual with a pathogenic STK11 mutation is 50%. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation in the family is known

About kjmonahan

Service lead for Family History of Bowel Cancer Clinic

Discussion

5 thoughts on “Peutz-Jeghers Syndrome (PJS)

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