Marfan syndrome:  from gene to therapy.
OBJECTIVE
Although historically Marfan syndrome (MFS) has always been considered as a condition caused by the deficiency of a structural extracellular matrix protein, fibrillin-1, the study of Marfan mouse models and Marfan-related conditions has shifted our current understanding to a pathogenic model that involves dysregulation of the cytokine-transforming growth factor beta (TGF-β) signaling.


RESULTS
In this review, we focus on the impact of the revised MFS clinical diagnostic criteria. We discuss lessons that have been learned from molecular findings in relevant Marfan-related conditions, such as sporadic thoracic aortic aneurysm/dissection, stiff skin syndrome, acromelic dysplasias and Loeys-Dietz syndrome. We explore the latest insights into the role of the alternative TGF-β signaling pathways in MFS pathogenesis. Finally, we give an update on the current and future treatment strategies.


CONCLUSIONS
The recent insights into the pathogenesis of MFS and related disorders have offered a prime example of translational medicine with immediate bridge between molecular findings and therapeutic options.
Laboratory for Aneurysmal Disease Research, Center for Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Nikhita
N
Bolar
Lut
L
Van Laer
Bart L
BL
Loeys
D000172:Acromegaly / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000293:Adolescent; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse