Abstract
Genetic aortic diseases are a group of illnesses characterized by aortic aneurysms or dissection in the presence of an underlying genetic defect. They are part of the broader spectrum of heritable thoracic aortic disease, which also includes those cases of aortic aneurysm or dissection with a positive family history but in whom no genetic cause is identified. Aortic disease in these conditions is a major cause of mortality, justifying clinical and scientific emphasis on the aorta. Aortic valve disease and atrioventricular valve abnormalities are known as important additional manifestations that require careful follow-up and management. The archetype of genetic aortic disease is Marfan syndrome, caused by pathogenic variants in the Fibrillin-1 gene. Given the presence of fibrillin-1 microfibers in the myocardium, myocardial dysfunction and associated arrhythmia are conceivable and have been shown to contribute to morbidity and mortality in patients with Marfan syndrome. In this review, we will discuss data on myocardial disease from human studies as well as insights obtained from the study of mouse models of Marfan syndrome. We will elaborate on the various phenotypic presentations in childhood and in adults and on the topic of arrhythmia. We will also briefly discuss the limited data available on other genetic forms of aortic disease.
Highlights
AND DEFINITION OF THE DISEASES: MARFAN SYNDROME AND HERITABLE THORACIC AORTIC DISEASEHeritable Thoracic Aortic Diseases (HTAD) encompasses a spectrum of genetic conditions in which aortic disease has an underlying genetic trigger or familial occurrence
The genetic causes fall into several distinct groups of genes coding for (I.) components of the extracellular matrix (ECM) (FBN1, COL3A1, LOX); (II.) components involved in the TGFβ pathway (TGFBR1 and 2, SMAD2 and 3 and TGFB2 and 3); and (III.) components of the vascular smooth muscle cell apparatus (ACTA2, MYLK, MYH11, PRKGA1) [1]
Marfan syndrome (MFS) is an inherited connective tissue disease caused by pathogenic variants in the Fibrillin-1 gene (FBN1), which codes for the ECM protein fibrillin-1
Summary
Edited by: Elena Cervi, Great Ormond Street Hospital for Children NHS Foundation Trust, United Kingdom. Genetic aortic diseases are a group of illnesses characterized by aortic aneurysms or dissection in the presence of an underlying genetic defect They are part of the broader spectrum of heritable thoracic aortic disease, which includes those cases of aortic aneurysm or dissection with a positive family history but in whom no genetic cause is identified. Aortic disease in these conditions is a major cause of mortality, justifying clinical and scientific emphasis on the aorta. We will discuss data on myocardial disease from human studies as well as insights obtained from the study of mouse models of Marfan syndrome.
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