Segmentale Überwuchssyndrome

Zusammenfassung

In den letzten Jahren wurden einige segmentale Überwuchssyndrome genetisch weiter aufgeklärt. Es handelt sich um sehr seltene Erkrankungen, deren Phänotypen über viele Jahre nicht eindeutig voneinander abgegrenzt werden konnten. Vom Überwuchs betroffen können das Skelettsystem, das Fett- und Bindegewebe, aber auch ganze Extremitäten und Organe sein. Beim Proteus-Syndrom sind somatische, aktivierende Mutationen im AKT1-Gen gefunden worden. Bei den PROS „PI3K related overgrowth spectrum“-Syndromen wie dem CLOVE-, dem Fibroadipösen Hyperplasie-Syndrom und dem Klippel-Trénaunay-Syndrom wurden Mutationen in der Kinase PI3KCA beschrieben. Auch hier ist die Mutation somatisch, d. h. im betroffenen Gewebe zu finden. Mutationen in der Keimbahn von PTEN führen zu den PTEN-Hamartom-Tumor-Syndromen, wie dem Cowden-, dem Bannayan-Riley-Ruvalcaba(BRR) und dem SOLAMEN-Syndrom. Letztendlich muss die Überprüfung der Mutationen aus dem mTOR-Signalweg eine abschließende Diagnose erbringen. Die Erkenntnisse über die Genetik der segmentalen Überwuchssyndrome bringen Grundlagen für neue therapeutische Ansätze mit mTOR-Inhibitoren, wie z. B. Sirolimus. Aktuell wird eine klinische Studie (SIPA-SOS) in Deutschland hierzu vorbereitet.

Summary

Recently, the genetic background of several segmental overgrowth syndromes has been described. The phenotypes of these rare diseases are overlapping and therefore, it has been difficult to discriminate them from each other for a long time. The overgrowth can be present at the skeletal system and at the soft tissue such as fat and connective tissue. The Proteus syndrome results from somatic mutations in AKT1. The PROS „PI3K related overgrowth spectrum“ syndromes such as the CLOVE, the Fibroadipose Hyperplasia syndrome and the Klippel-Trénaunay syndrome are caused by PI3KCA mutations. Again, these are somatic mutations and can only be found in the affected tissue. Germline mutations in PTEN result in PTEN-Hamartoma-Tumor syndromes such as the Cowden-, the Bannayan-Riley-Ruvalcaba- (BRR) and the SOLAMEN syndrome. Therefore, analyzing the mTOR signaling pathway will finally lead to the diagnosis. These new genetic findings give the background for a new therapeutic approach in segmental overgrowth syndromes using mTOR inhibitors such as Sirolimus. A clinical trial (SIPA-SOS) is in preparation in Germany.

Schlüsselwörter

Proteus-Syndrom - CLOVE-Syndrom - PTEN - AKT1 - PI3KCA - Lipomatose - Überwuchs

Keywords

Proteus syndrome - CLOVE syndrome - PTEN - AKT1 - PI3KCA - lipomatosis - overgrowth

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