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Peutz-Jeghers syndrome (PJS) is an inherited gastrointestinal disorder characterized by development of characteristic hamartomatous polyps throughout the gastrointestinal (GI) tract, and by mucocutaneous pigmentation. PJS carries a considerably increased risk of GI and extra-GI malignancies.
Prevalence estimates range from 1/25,000 to 1/300,000 births in the United States.
Despite high variability between families, characteristic PJS polyps generally occur in childhood and early adulthood, with onset often during the first 10 years of life. Hamartomatous polyps can occur at any site in the GI tract, but are most frequent in the small intestine. Other sites include the stomach, large intestine, nares, and rarely the renal pelvis, urinary bladder, and lungs. Although benign, polyps can lead to complications including bowel obstruction, rectal prolapse, and severe GI bleeding with secondary anemia, and intussusception. Adenomas may also occur. During infancy or childhood, patients develop dark blue to dark brown macules around the mouth, eyes, nares, and in the perianal area and buccal mucosa. Hyperpigmentation may also be found on the fingers and toes. The lesions may fade in adolescence and adulthood but tend to persist in the buccal mucosa. They can cause psychological stress. GI and extra-GI malignancies mainly concern adult patients and include colorectal and gastric cancer (estimated lifetime risk (LTR) of 15% by 50 years of age, and 57% by 70 years), pancreatic cancer (LTR 5% by 50 years of age, and 17% by 70 years), and breast and ovarian cancer in females (LTR 8% by 40 years of age, and 32% by 60 years of age). Female patients may also develop adenoma malignum of the cervix, and typically benign bilateral multifocal sex cord tumors with annular tubules (SCTAT). Males have a higher risk of large-cell calcifying Sertoli cell tumor (LCCSCT) (see these terms).
PJS is caused by a germline mutation in the STK11 gene (19p13.3). Mutations in this tumor suppressor gene are found in more than 80% of affected families.There are no clear genotype-phenotype correlations. One study showed that individuals with missense mutations had a significantly later time to onset of first polypectomy and of other symptoms compared with those either with truncating mutations or no detectable mutation. However in another study, the genotype-phenotype correlation was not observed.
Diagnosis is based on clinical findings and can be made in a patient presenting one of the following signs: two or more histologically confirmed PJ polyps, any number of PJ polyps and a family history of PJS, characteristic mucocutaneous pigmentation and a family history, or any number of PJ polyps associated with characteristic mucocutaneous pigmentation. Molecular genetic testing of the STK11 gene confirms the diagnosis and is available clinically.
Differential diagnoses include juvenile polyposis syndrome, hereditary mixed polyposis syndrome, the PTEN hamartoma tumor syndromes, and Carney complex (see these terms).
Prenatal diagnosis for increased risk pregnancies is available provided that the disease-causing mutation has been identified in the family.
Peutz-Jeghers syndrome is inherited in an autosomal dominant manner. The number of cases related to de novo gene mutations is not known. About 50% of cases appear to involve a single family member.
Management and treatment
Routine treatment methods should be used for polyp resection, intussusception and malignancies. Although generally recommended, there is no control data on the value of surveillance strategies in PJS patients. The aim of surveillance is to reduce polyp related complications in younger patients and to monitor malignancies in older patients.
The prognosis depends on the severity of polyp complications and on the development of malignancies.