What is the aorta?
The aorta is the largest artery in the body and carries blood away from the heart to the rest of the body (Figure 1).
The size of the aorta is dependent upon one’s age, sex, and body size. Disorders of the aorta often cause the aorta to enlarge or dilate. When the aorta enlarges significantly, this is called an aortic aneurysm (Figure 2). An aortic aneurysm in the chest cavity is known as a thoracic aortic aneurysm.
The wall of the aorta has 3 layers (Figure 4). One function of the aorta wall is to maintain the strength of the aorta.
What are the causes of thoracic aortic aneurysms?
There are many causes of thoracic aortic aneurysms. Aortic aneurysms may be due to acquired conditions such as degenerative (due to atherosclerosis) disease or inflammatory conditions (such as aortitis or infections) or may be related to an underlying genetic aortic condition (known as a hereditary or heritable aneurysm). Hereditary thoracic aortic aneurysm conditions may be passed from a parent to a child (Figure 4).
Hereditary thoracic aortic aneurysm conditions lead to abnormal structure and strength of the aortic wall and cause the aortic wall to weaken and lead to aneurysm formation.Thoracic aortic aneurysm can be seen by echocardiogram (shown in Figure 5), CT scan or MRI.
How are genetic factors involved?
The basic unit of heredity is a gene.A gene is a section of DNA with a specific function (Figure 7). Our genes provide instructions for the proper development and function of our body’s organ systems. A harmful change in the DNA of one gene is called a pathogenic variant (or mutation) (Figure 8).
A mutation in a gene can cause a person to develop an aortic aneurysm or aortic dissection. The GenTAC Alliance has as one of its missions to further research and education about genetically triggered (hereditary or heritable) thoracic aortic aneurysm conditions.
A single mutation in a gene can cause one or multiple physical changes in the body. When a genetic mutation leads to a recognizable pattern of changes in the body, the condition is called a syndrome. One example of a syndrome is Marfan syndrome that is caused by a pathogenic variant (mutation) in the FBN1 gene. In Marfan syndrome, one can recognize physical features including tall stature, elongated arms and legs, chest wall deformities, nearsightedness, dislocation of the eye lenses, etc.
What are the more common heritable thoracic aortic aneurysm conditions?
Some hereditable thoracic aortic aneurysm conditions cause aneurysm disease but do not lead to other outward features of a syndrome while others do cause changes in outward appearance.
- Marfan syndrome is caused by mutations in the FBN1 gene, the gene that makes the important connective tissue protein, fibrillin-1.
- Loeys-Dietz syndrome is caused by a pathogenic variant (mutation) in one of several genes (TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3) that are important in the TGF-β signaling pathway.
- Vascular Ehlers-Danlos syndrome is caused by pathogenic variants in the COL3A1 gene, a gene that makes a specific type of collagen.
- Familial thoracic aortic aneurysms (FTAA) or familial thoracic aortic aneurysm and dissections (FTAAD) are conditions caused by pathogenic variants in genes that lead to aortic aneurysm or aortic dissections. Generally, these conditions do not cause physical changes in other parts of the body, but in some individuals may lead to brain (cerebral) aneurysms. Multiple different genes have been identified to lead to FTAA, including many of the genes that also cause the syndromes mentioned above.
- Turner syndrome is a genetic condition in which a female is born with only one X-chromosome or is missing parts of the X chromosome. Individuals with Turner syndrome have an increased risk of bicuspid aortic valve as well as diseases of the aorta (aortic aneurysm and aortic coarctation).
- Bicuspid aortic valve (BAV) is the condition in which the aortic valve is made up of only 2 leaflets instead of the normal 3-leaflet valve. BAV is associated with important aortic diseases including ascending thoracic aortic aneurysm, coarctation of the aorta and aortic dissection. While the great majority of people with BAV and aneurysm disease are not found to have a genetic mutation, BAV disease may run in families.
Genetic testing is available for genetically triggered thoracic aortic conditions and may be very important in the evaluation and management of many of these conditions. Please click this link to learn more about genetic testing in hereditary thoracic aortic aneurysm disease (HTAD).
Because all of these conditions can lead to a weakening of the aortic wall leading to an aortic aneurysm and/or a risk of an aortic dissection, there are important recommendations about medical care, surgery and lifestyle modifications that apply to people with hereditary thoracic aortic aneurysm conditions. Please see each section for general guidelines.
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