Peutz-Jeghers syndrome

Last revised by Calum Worsley on 24 Oct 2022

Peutz-Jeghers syndrome is one of the polyposis syndromes. It has an autosomal dominant inheritance and is characterized by:

  • multiple hamartomatous polyps, most commonly involving the small intestine (predominantly the jejunum), but also colon and stomach; mouth and esophagus are spared

  • mucocutaneous melanin pigmentation involving the mouth, fingers and toes

Peutz-Jeghers syndrome has been reported to be as common as 1 in 8300 live births.

Findings on clinical examination include mucocutaneous hyperpigmented macules of the nose, buccal mucosa, axilla, hands, feet and genitalia 4. A clinical diagnosis can be made following histopathological confirmation of typical Peutz-Jeghers syndrome morphology in 2 or more intestinal polyps or after any number of polyps or hyperpigmented macules (in a characteristic location) with a positive family history 4.

Peutz-Jeghers polyps are non-neoplastic hamartomas due to the proliferation of all three layers of the mucosa, which have a characteristic feature of a smooth muscle core continuous with muscularis mucosa in a tree-like branching pattern. This distinguishes them from the hamartomatous polyps of Cronkhite-Canada syndrome, juvenile polyposis and Cowden disease 1.

Patients are at increased risk of:

  • intussusception

  • GI tract adenocarcinoma, although the polyps themselves are not premalignant

    • colorectal: 39%  lifetime risk 5

    • stomach: 29% lifetime risk 4​

    • small intestine: 13% lifetime risk 4

  • extraintestinal malignancies

    • adenoma malignum (adenocarcinoma subtype of the cervix)

    • breast: 45-50% lifetime risk 4, more frequently ductal

    • pancreas: 11-36% lifetime risk 4

    • ovary: 18-21% lifetime risk 4, mainly sex cord tumors

    • uterus: 9-10% lifetime risk 4

    • cervix: 10-23% lifetime risk 4

    • testis: 9% lifetime risk 4, large calcifying Sertoli cell tumors

    • lung: 15-17% lifetime risk 4

It is attributed to mutations in tumor suppressor genes, most commonly STK11 (70-94%) 4.

Due to the increased risk of malignancy, screening is generally recommended. Examples include annual mammography and contrast-enhanced breast MRI, beginning at 25 years of age; baseline CT/MR enterography at 8-10 years of age (and every 2-3 years from 18 years of age); MRCP or endoscopic US every 1-2 years beginning from 30-35 years of age 4.

The syndrome is named after Jans Peutz (1886-1957), a Dutch physician and Harold Jeghers (1904-1990), an American physician who had successively described the association between polyposis and the mucocutaneous macules.

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