Genetics of TAAD

Genetics of Thoracic Aortic Aneurysm and/or Dissection (TAAD)

The following classifications may help you determine you or your family’s genetic risk of TAAD:

  1. Syndromic TAAD: May be a result of a known genetic connective tissue disorder (Marfan, Loeys-Dietz, Ehlers-Danlos, or Turner syndrome)
  2. Familial Thoracic Acortic Aneurysm and/or Dissection (FTAAD): If you have a positive family history (1+ first degree relative(s) with TAAD)
  3. Sporadic TAAD: If you are the only person in your family to have TAAD with no family history of aortic aneurysms or dissections. Aortic screening is recommended for all 1st degree relatives (parents, children, and siblings)

Genetic Syndromes

Genetic syndromes are genetic diseases that affect more than one system, and some of these syndromes increase the risk for thoracic aortic aneurysm and dissection.  Disorders that confer this increased risk for TAAD include:

Marfan syndrome:  A life-threatening genetic disorder that affects connective tissue, which helps to hold the body’s cells and tissues together. This is caused by a mutation in the gene FBN1 which codes for the protein fibrillin-1. The main features of Marfan syndrome can affect the heart, blood vessels, bones, joints, and is found in about 1 in every 5,000 people. Common symptoms include long arms, legs and fingers, curved spine, flat feet, flexible joints, crowded teeth, curved spine, and/or stretch marks unrelated to weight change.

Loeys-Dietz syndrome:  is a genetic connective tissue disorder that is caused by a mutation in one of five genes including (TGFβR1, TGFβR2, SMAD-3, TGFβ2, and TGFβ3). Individuals with LDS can experience a variety of features involving the cardiovascular, musculoskeletal, skin and/or gastrointestinal systems. Some common symptoms include but are not limited to aneurysms (dilation of arteries), arterial tortuosity (twisting of arteries), widely spaced eyes, and split or broad uvula (the little flesh found hanging in the back of the mouth).

Ehlers-Danlos syndrome, vascular type: A genetic connective tissue disorder that is caused by defects in a protein called collagen. This defect is caused by alterations in the gene COL3A1. Common symptoms include thin, translucent skin, bruising easily, characteristic facial appearance (thin lips, small chin, thin nose, large eyes), and fragile arteries, muscles and internal organs.

Turner syndrome: A chromosomal disorder in which a female is born with complete or partial absence of the second X chromosome (sex chromosome). The most common feature of this condition is short stature which becomes noticeable from a young age of around 5. Lack of ovarian development is also commonly found in women with Turner’s syndrome; however, other symptoms and characteristics may also be present or vary. This disorder occurs in approximately 1 out of every 2,000 to 4,000 female births.

To learn more about these syndromes, please visit Patient Resources for links to the associated Foundation websites.

Familial Thoracic Aortic Aneurysm and/or Dissection (FTAAD)

Thoracic aortic aneurysm and/or dissection (TAAD) can run in families even when no genetic syndrome like Marfan syndrome is present in affected family members.  In these families, multiple people develop TAAD due to an underlying genetic change or mutation.  These families have Familial Thoracic Aortic Aneurysm and/or Dissection (FTAAD).  In families with FTAAD:

Unlike syndromes such as Marfan syndrome, there are typically no outward features to suggest that people with FTAAD have inherited a predisposition for thoracic aortic disease.  Generally, the only disease manifestation is the aortic disease, which is often asymptomatic until there is an aortic rupture or dissection.  This is why family history and aortic imaging are so important in helping identify people at risk for aortic disease.

Several genes have been identified to cause FTAAD including:  ACTA2 MYH11, FBN1, TGFBR1, and TGFBR2. Mutations in any one of these genes can cause a predisposition to develop TAAD to be inherited in a family.

Changes in these genes only explain the family history of FTAAD in 25-30% of families affected with FTAAD. We are currently working to identify the genes responsible for disease in the remaining 70-75% of cases.

 


 

 

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