Peutz-Jeghers syndrome

The estimated prevalence is 1/25,000 to 1/280,000. Birth-prevalence estimates vary widely across populations.

Peutz-Jeghers syndrome is inherited in an autosomal dominant manner. Each first-degree relative of an affected individual has a 50 % risk of inheriting the familial pathogenic variant. De novo pathogenic variants account for approximately 40% of probands in one published series. Prenatal molecular testing is technically possible once the familial pathogenic variant has been identified.

The clinical diagnosis of Peutz-Jeghers syndrome is established using the ; meeting these criteria establishes a clinical diagnosis. Histopathological identification of PJS-type hamartomatous polyps, characterised by interdigitating smooth-muscle bundles in an arborising pattern within the lamina propria, supports the diagnosis. Small-bowel evaluation using video capsule endoscopy or magnetic resonance enterography is recommended for the detection and surveillance of polyps.

Main differential diagnoses include:

• (JPS): juvenile-type polyps presenting by age 20 years without mucocutaneous pigmentation; BMPR1A, SMAD4
• : polyposis with trichilemmomas, macrocephaly, and breast, thyroid, and endometrial cancers; PTEN
• (FAP): adenomatous colorectal polyposis with desmoid tumours, osteomas, and CHRPE; APC

• Establishing the molecular diagnosis confirms the clinical suspicion and enables appropriate counselling and care planning.
• Identification of the underlying pathogenic variant enables condition-specific surveillance, including early cancer detection programmes, which is a prerequisite for targeted medical care; decisions on intensity and timing rest with the treating physicians in consultation with the affected individual.
• Predictive testing of at-risk relatives can identify family members who carry the familial pathogenic variant, allowing those who test positive to access surveillance and informed reproductive counselling.

• McGarrity TJ, Amos CI, Baker MJ. Peutz-Jeghers Syndrome. 2001 Feb 23 [Updated 2021 Sep 2]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from:
• Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010;59(7):975-86. doi: 10.1136/gut.2009.198499. PMID: .
• Wagner A, Aretz S, Auranen A, Bruno MJ, Cavestro GM, Crosbie EJ, et al. The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline. Journal of clinical medicine. 2021;10(3). doi: 10.3390/jcm10030473. PMID: . PMCID: PMC7865862.