Peutz-Jeghers syndrome

Last reviewed: 26 Aug 2022

Last updated: 31 Jan 2019

Peutz-Jeghers syndrome is associated with an increased risk of intestinal cancer (e.g., colorectal and small bowel) and extra-intestinal cancer (e.g., breast, pancreas). The lifetime risk for developing cancer is estimated to be up to 93%. Unusual genital tract tumours may occur.

Patients require lifelong cancer surveillance with prophylactic polypectomy.

Small bowel obstruction is a frequent complication; up to 70% of individuals require laparotomy for small bowel obstruction by the age of 18 years.

Definition

Peutz-Jeghers syndrome (PJS) is a rare, autosomal-dominant disorder characterised by hamartomatous polyposis caused by germline mutations in the STK11 (LKB1) gene. Mutations are found in about 93% of individuals with PJS, and may be inherited in an autosomal-dominant manner or occur de novo. The defining features are mucocutaneous pigmentation and gastrointestinal polyposis. The lifetime cancer risk is reported to be as high as 90%, including gastrointestinal and extra-intestinal malignancies. Breast, colorectal, and pancreatic malignancies occur most frequently.[1]

History and exam

Key diagnostic factors

presence of risk factors
small intestinal obstruction
mucocutaneous pigmentation

More key diagnostic factors

Other diagnostic factors

abdominal discomfort and distension
abdominal pain
gastrointestinal bleeding
polyp prolapse per anus
enlarged testicles (without masses)
bilateral gynaecomastia
fatigue
pallor
signs of cardiac failure

Other diagnostic factors

Risk factors

positive family history
germline STK11 gene mutation

More risk factors

Diagnostic investigations

1st investigations to order

endoscopy
polyp histology
STK11 genetic testing

More 1st investigations to order

Treatment algorithm

ACUTE

initially confirmed polyposis: symptomatic or asymptomatic

ONGOING

following initial surveillance colonoscopy

Contributors

Authors

Brandie Heald, MS, LGC

Licensed Genetic Counselor

Genomic Medicine Institute

Sanford R. Weiss Center for Hereditary Colorectal Neoplasia

Cleveland Clinic

Cleveland

Disclosures

BH declares that she has received payment from the following but has no contractual agreement to disseminate product information for them: Speakers Bureau Myriad Genetics Lab, and the advisory board for Invitae. BH is also President of the Collaborative Group of the Americas on Inherited Colorectal Cancer, for which she does not receive payment.

James Church, MD

Victor W. Fazio Chair

Department of Colorectal Surgery

Digestive Disease Institute

Cleveland Clinic

Director

Sanford R. Weiss MD Center for Hereditary Colorectal Neoplasia

Cleveland Clinic

Cleveland

Disclosures

JC declares that he has no competing interests.

Carol A. Burke, MD, FACP, FACG, FASGE

Director

Center for Colon Polyp and Cancer Prevention

Department of Gastroenterology and Hepatology

Associate Director

Sanford R. Weiss Center for Hereditary Colorectal Neoplasia

Section of Polyposis

Digestive Disease Institute

Cleveland Clinic

Cleveland

Disclosures

CAB receives research support from Cancer Prevention Pharmaceuticals.

Peer reviewers

Daniel Von Allmen, MD

Chief of Pediatric Surgery

University of North Carolina

Chapel Hill

Disclosures

DVA declares that he has no competing interests.

Patrick Morrison, MD

Consultant in Clinical Genetics

Department of Medical Genetics

Belfast HSC Trust

Belfast

Disclosures

PM declares that he has no competing interests.

Differentials
- Juvenile polyposis syndrome
- PTEN-hamartoma tumour syndrome
- Mixed hereditary polyposis syndrome
More Differentials
Guidelines
- NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal
- Clinical practice guidelines for the prevention, early detection and management of colorectal cancer
More Guidelines
Patient leaflets
Bowel cancer: what is it?
Bowel cancer: what treatments work?
More Patient leaflets
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Peutz-Jeghers syndrome

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Treatment algorithm

initially confirmed polyposis: symptomatic or asymptomatic

following initial surveillance colonoscopy

Contributors

Authors

Brandie Heald, MS, LGC

Disclosures

James Church, MD

Disclosures

Carol A. Burke, MD, FACP, FACG, FASGE

Disclosures

Peer reviewers

Daniel Von Allmen, MD

Disclosures

Patrick Morrison, MD

Disclosures

Differentials

Guidelines

Patient leaflets

Log in or subscribe to access all of BMJ Best Practice

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