DISEASE CHARACTERISTICS:
Peutz-Jeghers syndrome (PJS) is characterized by the association of gastrointestinal polyposis and mucocutaneous pigmentation. 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. 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:
Treatment of manifestations: Routine endoscopic and intraoperative enteroscopy with polypectomy to decrease the frequency of emergency laparotomy and bowel loss resulting from intussusception; consider using wireless capsule endoscopy to diagnose small-bowel polyps and double-balloon ("push and pull") enteroscopy to eradicate small-bowel polyps without laparotomy. Removal of small bowel polyps by laparoscopic-assisted double balloon enteroscopy avoids enterostomy and the bowel loss that occurs with standard treatment of malignancies; conservative management of gonadal tumors in males and females. Surveillance: Protocols have been suggested for monitoring stomach, small and large bowel, breasts, testicles, ovaries, uterus, and pancreas by various procedures as early as age eight years and as frequently as once a year. 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
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