Genes Associated with Thoracic Aortic Aneurysm and Dissection

Abstract

Thoracic aortic aneurysm (TAA) is a lethal disease, with a natural history of enlarging progressively until dissection or rupture occurs. Since the discovery almost 20 years ago that ascending TAAs are highly familial, our understanding of the genetics of thoracic aortic aneurysm and dissection (TAAD) has increased exponentially. At least 29 genes have been shown to be associated with the development of TAAD, the majority of which encode proteins involved in the extracellular matrix, smooth muscle cell contraction or metabolism, or the transforming growth factor-β signaling pathway. Almost one-quarter of TAAD patients have a mutation in one of these genes. In this review, we provide a summary of TAAD-associated genes, associated clinical features of the vasculature, and implications for surgical treatment of TAAD. With the widespread use of next-generation sequencing and development of novel functional assays, the future of the genetics of TAAD is bright, as both novel TAAD genes and variants within the genes will continue to be identified.

Aortic Size and Aortic Dissection: Does One Size Fit All?

“…In patients with heritable disorders of connective tissue prone to aortic dilatation, dissection, and rupture, such as Marfan syndrome, Ehlers-Danlos syndromes, adult polycystic kidney disease, and others, the structure of the aortic wall is mostly genetically determined. Furthermore, approximately 20% of patients with a thoracic aortic aneurysm not related to a heritable connective tissue disorder have an affective family member suggesting that genetic predisposition is present in these patients [13,14,15]. Recently, Brownstein et al [15] published a state of the art article, reporting known gene abnormalities related to aortic dilatation, dissection, and rupture.…”

“…Furthermore, approximately 20% of patients with a thoracic aortic aneurysm not related to a heritable connective tissue disorder have an affective family member suggesting that genetic predisposition is present in these patients [13,14,15]. Recently, Brownstein et al [15] published a state of the art article, reporting known gene abnormalities related to aortic dilatation, dissection, and rupture.…”

“…The effects of this surgery on V-V flow, aortic function, and progression of aortic size are not yet well defined. More recently, it has been shown that in certain heritable diseases associated with aortic aneurysm, V-V flow may be defective [14,15]. …”

“…At present, a mosaic approach is necessary since the population in which aortic dissection occurs is nonhomogeneous, and so several parameters have to be taken into consideration. To make a rational clinical decision, the size at which the aorta dissects has to be defined in each subgroup in which dissections commonly occur, and the indications for therapeutic intervention should be based on this information [15,29]. Family history, arterial survey, arterial hypertension, aortic size and progression of aortic size, aortic function, inflammatory processes of the aortic wall that play an important role in the progression of aortic size, gene mutations, genetic biomarkers, V-V flow, hemodynamic factors, and triggers of aortic dissection must all be considered for each individual patient, as it is obvious that one aortic size does not apply to all (Fig.…”

Natural history of aortic root aneurysms in Marfan syndrome

“…These two patients were included in this study since they met the aortic and systemic score criteria of MFS, expressed the FBN-1 mutation, and had none of the discriminating features of EDS or LDS described in the Ghent nosology (18). Such findings of non-MFS mutations in patients diagnosed clinically with MFS are being increasingly recognized in the present era of whole exome sequencing (WES) for aortic disease patients (19).…”