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Familiäre adenomatöse Polyposis und andere Polyposissyndrome

Familial adenomatous polyposis and other polyposis syndromes

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Zusammenfassung

Die adenomatöse Polyposis coli wird je nach Anzahl der Adenome in die klassische (FAP), die attenuierte Form (AFAP) und die atypische Form (ATFAP) eingeteilt. Autosomal-dominant vererbte Mutationen im APC-Gen finden sich bei 80% der Patienten mit FAP, autosomal-rezessiv vererbte Mutationen in MUTYH (MUTYH-assoziierte Polyposis, MAP) führen häufig zu einer AFAP. Bei der MAP können neben Adenomen auch hyperplastische Polypen oder serratierte Adenome vorliegen, extraintestinale Manifestationen finden sich vor allem bei der FAP. Die Nachkommen von FAP-Patienten haben ein Risiko von 50%, welches bei der MAP unter 1% liegt. Hyperplastische Polyposissyndrome (HPS) können familiär gehäuft auftreten, molekular kann man in Abhängigkeit von somatischen Mutationen in BRAF oder KRAS im Polypengewebe derzeit drei Pathways unterscheiden. Die kausale Genetik ist ungeklärt, für Verwandte ersten Grades ist eine Risikoerhöhung auszusprechen. Die Genetik der juvenilen Polypose ist weitgehend geklärt, bei den hamartomatösen Polyposen (Peutz-Jeghers- und Cowden-Syndrom) können derzeit etwa 50% der Fälle genetisch geklärt werden. Vor allem bei hamartomatösen Polyposissyndromen sind die Risiken für extraintestinale Tumorerkrankungen zu berücksichtigen.

Abstract

The number of adenomas allows the clinical differentiation of familial adenomatous polyposis into the classical (FAP), attenuated (AFAP), and atypical (ATFAP) forms. Mutations in the APC gene are found in 80% of FAP patients, with inheritance being autosomal dominant. Mutations in MUTYH (MUTYH-associated polyposis, or MAP) follow a recessive inheritance and clinically dominate AFAP. MAP is associated with adenomas, but hyperplastic polyps and serrated adenomas can also be prevalent. Extraintestinal manifestations are associated with FAP. The recurrence risk for FAP is 50% and is below 1% for MAP. Hyperplastic polyposis syndromes (HPS) can show a familial occurrence; mutation analysis of the polyp tissue allows preliminary subdivision into cases with mutations of either BRAF or KRAS and cases with no mutation in either of these genes. The genetic predisposition of HPS in the germline is thus far unknown. The genetics of juvenile polyposis has been established; hamartomatous polyposis syndromes (Peutz–Jeghers and Cowden syndromes) show a 50% mutation detection rate. Especially in hamartomatous polyposis syndromes, the risk for extraintestinal cancers needs to be considered.

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Authors and Affiliations

  1. Medizinisch Genetisches Zentrum München, Bayerstr. 3-5, 80335, München, Deutschland

    E. Holinski-Feder & M. Morak

  2. Medizinische Klinik, Campus Innenstadt, LMU München, München, Deutschland

    E. Holinski-Feder & M. Morak

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  1. E. Holinski-Feder
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  2. M. Morak
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Correspondence to E. Holinski-Feder.

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Holinski-Feder, E., Morak, M. Familiäre adenomatöse Polyposis und andere Polyposissyndrome. Gastroenterologe 5, 7–15 (2010). https://doi.org/10.1007/s11377-009-0342-y

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