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Peutz-Jeghers syndrome: Epidemiology, clinical manifestations, and diagnosis

Anthony J Lembo, MD
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Peutz-Jeghers syndrome (PJS) is an autosomal dominant syndrome characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and an increased risk of gastrointestinal and nongastrointestinal cancer [1-3].

This topic will review the genetic basis, clinical manifestations, and diagnosis of PJS. The management of PJS and other familial hamartomatous polyposis syndromes of the gastrointestinal tract (eg, juvenile polyposis, Cowden syndrome, and Bannayan-Riley Ruvalcaba syndrome) are discussed in detail, separately [4]. (See "Overview of colon polyps" and "Juvenile polyposis syndrome".)


Peutz-Jeghers syndrome (PJS) is rare with an estimated prevalence of 1:8000 to 1:200,000 births [5]. Males and females are equally affected.

PJS is an autosomal dominant disorder that is most often due to germline mutations in the STK11 (LKB1) gene encoding a serine threonine kinase mapped to chromosome 19p13.3 [6-8]. Germline mutations in STK11, a designated tumor suppressor gene in combination with an acquired genetic defect of the second STK11 allele in somatic cells, are responsible for the clinical manifestations of PJS [7-10]. PJS has a high penetrance of over 90 percent by the age of 30 years, but 10 to 20 percent of individuals with PJS have no family history and are presumed to have PJS due to de novo mutations [11].

STK11 appears to regulate cell polarity, an observation that may be important for explaining how hamartomas develop and the apparent paradox that PJS patients with benign hamartomatous polyps are at increased risk for cancer [12,13]. A traditional theory has been that, for unclear reasons, some hamartomas in patients with PJS proceed on a pathway to malignant transformation. However, an alternative theory suggests that dysregulation of cell polarization leads concurrently to a cancer predisposition while also creating a predisposition for mucosal prolapse [14]. Mucosal prolapse can lead to the development of polypoid lesions that are histologically similar to hamartomas. Thus, the hamartomas seen in PJS may be an epiphenomenon reflecting disruption of cell polarity pathways, which predisposes simultaneously to mucosal prolapse (and hamartoma formation) and cancer.

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Literature review current through: Nov 2017. | This topic last updated: Apr 01, 2014.
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