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Peutz-Jeghers syndrome

Identity

Note syndrome associating mucocutaneous melanotic pigmentation, intestinal polyposis, and an increased risk of cancers
Inheritance Autosomal dominant with a high penetrance; frequency is about 3.5/105 newborns; 1/3 to 1/2 of cases are new mutations.

Clinics

Phenotype and clinics
  • Skin numerous brown or bleuish mucocutaneous macules (melanin spots) , especially around the orifices (mouth, including the buccal mucosa, eyes, nostrils, anus, genitalia), on the hands, ... ; they tend to deseapear with age; (at puberty or in adulthood); Note: in patients with isolated mucocutaneous melanotic pigmentation (without polyps), the cancer risk is lower, and the genetic defect looks different.
  • Gastrointestinal tract (GI tract): polyps of amartomatous origin (with a characteristic arborization of nonstriated muscles) may be found in any portion of the GI tract with varying frequencies: from 95% to 15%: in the small bowel, jejunum, ileum, large intestin, rectum,stomach, and the duodenum; risk of intussusception, which may be cause of death; onset for symptoms occurs from the firstyear of life to elderness (median age10-25 years, somewhat earlier in male patients).; polyps of other organs can occur.
    • Neoplastic risk
  • Tumors develop, with a relative risk of 10-20, and a cumulative risk of more than 90% between ages 15 and 64; mean interval between the diagnosis of Peutz-Jeghers syndrome and the diagnosis of cancer is about 20 yrs..Cancers at risk are:
  • small intestin: 500 fold increase,
  • stomach:200 fold,
  • pancreas: 100,
  • colon: 85,
  • esophagus: 60,
  • ovary: 30, and the benign sex cord tumor with annular tubules
  • uterus, breast, lung: 15 to 20
    • Treatment surveillance with endoscopic (GI tract) and gynecologic regular screenings, surgery when necessary

    Genes involved and Proteins

     
    Gene NameSTK11
    Location 19p13.3
    Note mutations in STK11 is found in about 70 % of cases of Peutz-Jeghers syndrome; there is genetic heterogeneity, and yet undiscovered gene(s) may also be responsible for the disease
    DNA/RNA
    Description 10 exons
    Protein
    Function serine/threonine protein kinase
    Mutations
    Germinal most mutations in Peutz-Jeghers syndrome are null alleles; they are dispersed through the entire gene
    Somatic many of the polyps that develop in Peutz-Jeghers syndrome show loss of heterozygosity;

    External links

    OMIM175200
    OrphanetPeutz-Jeghers syndrome

    Bibliography

    A serine/threonine kinase gene defective in Peutz-Jeghers syndrome.
    Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Hˆglund P, Jˆ§rvinen H, Kristo P, Pelin K, Ridanpˆ§ˆ§ M, Salovaara R, Toro T, Bodmer W, Olschwang S, Olsen AS, Stratton MR, de la Chapelle A, Aaltonen LA
    Nature. 1998 ; 391 (6663) : 184-187.
    PMID 9428765
     
    Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase.
    Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Mˆºller O, Back W, Zimmer M
    Nature genetics. 1998 ; 18 (1) : 38-43.
    PMID 9425897
     
    STK11/LKB1 germline mutations are not identified in most Peutz-Jeghers syndrome patients.
    Jiang CY, Esufali S, Berk T, Gallinger S, Cohen Z, Tobi M, Redston M, Bapat B
    Clinical genetics. 1999 ; 56 (2) : 136-141.
    PMID 10517250
     
    Association of Peutz-Jeghers-like mucocutaneous pigmentation with breast and gynecologic carcinomas in women.
    Boardman LA, Pittelkow MR, Couch FJ, Schaid DJ, McDonnell SK, Burgart LJ, Ahlquist DA, Carney JA, Schwartz DI, Thibodeau SN, Hartmann LC
    Medicine. 2000 ; 79 (5) : 293-298.
    PMID 11039077
     
    Very high risk of cancer in familial Peutz-Jeghers syndrome.
    Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, Cruz-Correa M, Offerhaus JA
    Gastroenterology. 2000 ; 119 (6) : 1447-1453.
    PMID 11113065
     
    Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth.
    Sapkota GP, Kieloch A, Lizcano JM, Lain S, Arthur JS, Williams MR, Morrice N, Deak M, Alessi DR
    The Journal of biological chemistry. 2001 ; 276 (22) : 19469-19482.
    PMID 11297520
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Contributor(s)

    Written02-2002Jean-Loup Huret

    Citation

    This paper should be referenced as such :
    Huret JL . Peutz-Jeghers syndrome. Atlas Genet Cytogenet Oncol Haematol. February 2002 .
    URL : http://AtlasGeneticsOncology.org/Kprones/PeutzJeghersID10025.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Mon May 12 18:13:57 2008

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