title: Aetiology and management of hereditary aortopathy.
abstract: Aortic aneurysms are a major health problem because they account for 1-2% of all deaths in the Western population. Although abdominal aortic aneurysms (AAAs) are more prevalent than thoracic aortic aneurysms (TAAs), TAAs have been more exhaustively studied over the past 2 decades because they have a higher heritability and affect younger individuals. Gene identification in both syndromic and nonsyndromic TAA is proceeding at a rapid pace and has already pinpointed >20 genes associated with familial TAA risk. Whereas these genes explain <30% of all cases of familial TAA, their functional characterization has substantially improved our knowledge of the underlying pathological mechanisms. As such, perturbed extracellular matrix homeostasis, transforming growth factor-β signalling, and vascular smooth muscle cell contractility have been proposed as important processes in TAA pathogenesis. These new insights enable novel treatment options that are currently being investigated in large clinical trials. Moreover, together with the advent of next-generation sequencing approaches, these genetic findings are promoting a shift in the management of patients with TAA by enabling gene-tailored interventions. In this Review, we comprehensively describe the molecular landscape of familial TAA, and we discuss whether familial TAA, from a biological point of view, can serve as a paradigm for the genetically more complex forms of the condition, such as sporadic TAA or AAA.
authors.affiliation: Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650 Antwerp, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Verstraeten
authors.affiliation: Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650 Antwerp, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Luyckx
authors.affiliation: Centre of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650 Antwerp, Belgium.|Department of Human Genetics, Radboud University Nijmegen Medical Center, Geert Grooteplein-Zuid 10, 6525 Nijmegen, Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Loeys
mesh_terms: D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D020412:Multifactorial Inheritance; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018579:Patient Selection; D018570:Risk Assessment; D015398:Signal Transduction / Q000502:physiology