Hereditäre Erkrankungen mit Gelenkhypermobilität

Zusammenfassung

Unter Gelenkhypermobilität versteht man die Überbeweglichkeit eines oder mehrerer Gelenke. Hypermobilität ist oftmals mit extraartikulären Begleitmanifestationen vergesellschaftet und tritt gehäuft bei hereditären Erkrankungen des Bindegewebes und Skeletts, wie Marfan-Syndrom (MFS), marfanoiden Erkrankungen, Ehlers-Danlos-Syndrom (EDS), Osteogenesis imperfecta (OI) und weiteren Skelettdysplasien auf. Während das MFS durch Fibrillin-1 (FBN1)-Mutationen hervorgerufen wird, führen Mutationen in den TGFbeta-Rezeptoren TGFBR1 und TGFBR2 zum marfanähnlichen Loeys-Dietz-Syndrom (LDS). Untersuchungen an Mausmodellen und bei Patienten zeigen, dass eine erhöhte Verfügbarkeit von Transforming-Growth- Factor (TGF)-beta ein wichtiger Faktor bei der Pathogenese des MFS und LDS ist. Demgegenüber werden die unterschiedlichen EDS- und OI-Formen durch Mutationen verursacht, die die Synthese und Modifikation verschiedener fibrillärer Kollagene betreffen. In diesem Übersichtsartikel präsentieren wir eine aktuelle Zusammenfassung bedeutsamer klinischer und genetischer Erkenntnisse von hereditären Erkrankungen des Bindegewebes und Skeletts mit Gelenkhypermobilität.

Summary

Joint hypermobility refers to an increased mobility of one or more joints. Joint hypermobility is often associated with extraarticular manifestations and presents in connective tissue and skeletal disorders, including Marfan Syndrome (MFS), Ehlers-Danlos Syndrome (EDS), Osteogenesis imperfecta (OI) and a variety of skeletal dysplasias. Whereas MFS is caused by Fibrillin-1 (FBN1) mutations, mutations of the TGF beta receptors TGFBR1 and TGFBR2 cause the Loeys Dietz Syndrome (LDS). Analysis of mouse models and patients indicate that Transforming Growth Factor (TGF) beta plays an important role in the pathogenesis of MFS and LDS. In contrast, mutations of genes that affect the synthesis and modification of several fibrillary collagens lead to distinct EDS and OI forms. In this review we present a summary of important clinical and genetic findings of hereditary connective tissue and skeletal disorders with joint hypermobility.

Schlüsselwörter

Gelenkhypermobilität - Marfan-Syndrom - Ehlers-Danlos-Syndrom - Osteogenesis imperfecta

Keywords

Joint hypermobility - Marfan Syndrome - Ehlers- Danlos Syndrome - Osteogenesis imperfecta

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