title: TGF-β signalopathies as a paradigm for translational medicine.
abstract: This review focusses on impact of a better knowledge of pathogenic mechanisms of Marfan and related disorders on their treatment strategies. It was long believed that a structural impairment formed the basis of Marfan syndrome as deficiency in the structural extracellular matrix component, fibrillin-1 is the cause of Marfan syndrome. However, the study of Marfan mouse models has revealed the strong involvement of the transforming growth factor-β signalling pathway in the pathogenesis of Marfan. Similarly, this pathway was demonstrated to be key in the pathogenesis of Loeys-Dietz and Shprintzen-Goldberg syndrome. The elucidation of the underlying pathogenic mechanisms has led to new treatment strategies, targeting the overactive TGF-β pathway. Various clinical trials are currently investigating the potential new treatment options. A meta-analysis will contribute to a better understanding of the various trial results.
authors.affiliation: Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium. Electronic address: bart.loeys@uantwerpen.be.
authors.forename: Elyssa
authors.initials: E
authors.lastname: Cannaerts
authors.affiliation: Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Gerarda
authors.initials: G
authors.lastname: van de Beek
authors.affiliation: Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Verstraeten
authors.affiliation: Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
authors.affiliation: Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium; Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Loeys
mesh_terms: D000818:Animals; D054119:Arachnodactyly / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D057170:Translational Research, Biomedical
chemical_list: D016212:Transforming Growth Factor beta
keywords: Angiotensin receptor blocker; Beta blocker; Loeys-Dietz syndrome; Marfan syndrome; Shprintzen-Goldberg syndrome; Transforming growth factor beta