Peutz-Jeghers syndrome: clinicopathology and molecular alterations

Peutz-Jeghers syndrome (PJS, OMIM 175200) is an unusual inherited intestinal polyposis syndrome associated with distinct peri-oral blue/black freckling 1–9]. Variable penetrance and clinical heterogeneity make it difficult to determine the exact frequency of PJS 4]. PJS is a cancer predisposition syndrome. Affected individuals are at high risk for intestinal and extra-intestinal cancers. In 1997, linkage studies mapped PJS to chromosome 19p 10, 11], and subsequently a serine/threonine kinase gene defect (LKB1) was noted in a majority of PJS cases 12, 13]. A phenotypically similar syndrome has been produced in an LKB1 mouse knockout model 14–18]. Several PJS kindred without LKB1 mutations have been described, suggesting other PJS loci 19–22]. The management of PJS is complex and evolving. New endoscopic technologies may improve management of intestinal polyposis. Identification of specific genetic mutations and their targets will more accurately assess the clinical course, and help gage the magnitude of cancer risk for affected individuals. Received 20 February 2006; received after revision 5 May 2006; accepted 15 June 2006