Peutz-Jeghers syndrome: risks of a hereditary condition

Peutz-Jeghers syndrome (PJS) is a rare autosomal-dominant disorder characterized by hamartomatous polyposis of the gastrointestinal tract and melanin pigmentation of the skin and mucous membranes. We review the clinical features of PJS with special emphasis on the risks for its gene carriers.

Review of the literature.

Risks imposed by the presence of polyps in PJS patients include surgical emergencies like small bowel intussusception, and chronic or acute bleeding from the polyps. As the polyps in PJS are hamartomas, the disease had in the past always been thought not to have malignant potential. However, more and more reports suggest an association of PJS with both gastrointestinal and non-gastrointestinal tumours. Whether these malignancies originate from the polyps is not clear, but the frequent occurrence of some rare extra-intestinal malignancies such as tumours of the ovary (sex cord tumours with annular tubules), cervix (adenoma malignum) and testis (Sertoli cell tumours) indicates a general susceptibility for the development of malignancies. The PJS gene, which was recently identified to encode for the serine threonine kinase STK11, is therefore thought to act as a tumour-suppressor gene.

PJS gene carriers not only run risks of polyp-induced gastrointestinal complications, but also are at increased risk of developing cancer, both within and outside the gastrointestinal tract. As genetic identification of asymptomatic gene carriers in this relatively rare disorder becomes possible, surveillance and screening protocols need to be developed for PJS patients and their relatives.