title: Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery.
abstract: Marfan syndrome (MFS) is a rare, autosomal-dominant, multisystem disorder, presenting with skeletal, ocular, skin, and cardiovascular symptoms. Significant clinical overlap with other systemic connective tissue diseases, including Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS), and the MASS phenotype, has been documented. In MFS and LDS, the cardiovascular manifestations account for the major cause of patient morbidity and mortality, rendering them the main target for therapeutic intervention. Over the past decades, gene identification studies confidently linked the aforementioned syndromes, as well as nonsyndromic aneurysmal disease, to genetic defects in proteins related to the transforming growth factor (TGF)-β pathway, greatly expanding our knowledge on the disease mechanisms and providing us with novel therapeutic targets. As a result, the focus of the developing pharmacological treatment strategies is shifting from hemodynamic stress management to TGF-β antagonism. In this review, we discuss the insights that have been gained in the molecular biology of MFS and related disorders over the past 25 years.
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: Maaike
authors.initials: M
authors.lastname: Alaerts
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: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D054119:Arachnodactyly / Q000188:drug therapy / Q000235:genetics*; D003398:Craniosynostoses / Q000188:drug therapy / Q000235:genetics*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000188:drug therapy / Q000235:genetics*; D008382:Marfan Syndrome / Q000188:drug therapy / Q000235:genetics*; D008945:Mitral Valve Prolapse / Q000188:drug therapy / Q000235:genetics*; D009216:Myopia / Q000188:drug therapy / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D057911:Angiotensin Receptor Antagonists; D016212:Transforming Growth Factor beta
keywords: FBN1; LDS; Loeys-Dietz syndrome; MFS; Marfan syndrome; SKI; SMAD2; SMAD3; TGF-β signaling; TGFB2; TGFB3; TGFBR1; TGFBR2; thoracic aortic aneurysm