Genetics

Genetics 101: The First Step to Understanding Genetic Risks

Genes are the basic physical and functional units of heredity.  Genes are made up of DNA and act as instructions for our body to grow and develop properly.  The Human Genome Project has estimated that humans have between 20,000-25,000 genes.  Genes are stored in packages called chromosomes.

Every person has two copies of each gene, getting one copy from each parent.  The genes do not do the work in the cells; instead they tell the cells how to make proteins, which do the work (such as the collagens that provide strength to our skin and the enzymes that digest our food).  Most genes are the same in all people, but a small number of genes (less than 1%) are slightly different between people.  Small differences in the genes lead to small differences in the protein encoded by that gene, and contribute to each person’s unique physical features, including skin and hair color, but also how well the organs in our body work.

Some genetic changes are very rare and others are common in the population.  The genetic changes, also called mutations, that cause thoracic aortic aneurysms and dissections to be inherited, or run in families, are very rare.  It is important to note that genes themselves do not cause disease — genetic disorders are caused by mutations that make a gene, and subsequently the protein, function improperly.

A gene mutation is a permanent change, or alteration, in the DNA that makes up a gene.  They can be inherited from a parent or show up new in an individual.  Mutations that are passed from parent to child are called hereditary mutations.  This type of mutation is present throughout a person’s life in virtually every cell of the body.  Sometimes, genetic mutations prevent one or more genes from working properly.  By changing a gene’s instructions, a mutation can cause a normally-occurring protein to malfunction or be missing entirely.  When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition.  A condition caused by mutations in a gene is called a genetic disorder.

For more information about DNA, genes, and how they work, visit Genetics Home Reference: http://ghr.nlm.nih.gov/.

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

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, Loeys-Dietz syndrome, Ehlers-Danlos syndrome – vascular type, and Turner syndrome.  To learn more about these genetic conditions, please visit the following:

Marfan syndrome:  National Marfan Foundation

Loeys-Dietz syndrome:  Loeys-Dietz Syndrome Foundation

Ehlers-Danlos syndrome, vascular type:  Ehlers-Danlos National Foundation; EDS Network CARES Foundation

Turner syndrome:  Turner Syndrome Society of the United States

Familial Thoracic Aortic Aneurysm and/or Dissection (FTAAD)

Thoracic aortic aneurysm and/or dissection (abbreviated 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 typically are 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 to help identify people who are at risk for aortic disease.

There are five genes that are known to cause FTAAD:  ACTA2, responsible for 10-15% of FTAAD, MYH11 (1%), FBN1 (rare), TGFBR1 (1%), and TGFBR2 (2.5%).  Mutations in any one of these genes cause a predisposition to develop TAAD to be inherited in a family.

Note: Changes in these five genes only explain the family history of FTAAD in one-fifth, or 20%, of families affected with FTAAD.  We cannot identify the underlying genetic cause of FTAAD in 80% of families.  We need to continue ongoing research to find more genes and provide information to these families.

Clinical genetic testing of these genes is available through a clinical DNA diagnostic lab.  It is important that genetic testing be done with the guidance of a genetics professional (clinical geneticist or genetic counselor) so that families understand what the results mean (either positive or negative) for a change or mutation in one of these genes.  To find a local genetics provider in your area, visit the National Society of Genetic Counselors.

What should I do if I think that I or a family member may have FTAAD?

Family history is the most important tool to help evaluate a family for FTAAD.  If you have, or have had a thoracic aortic aneurysm or dissection, OR have a family history of aortic aneurysm or dissection:

  1. Talk to your primary care provider or a local genetics professional about your risk, the risk to your family members, and to determine if the thoracic aortic disease is due to a genetic syndrome.  You may also CONTACT US to discuss your family history.

Family members at risk for inheriting a predisposition for TAAD need aortic imaging.  First-degree relatives (parents, siblings, and children) of individuals with an aortic aneurysm or dissection should undergo aortic screening by echocardiogram (an ultrasound of the heart).  Tell your physician that you need aortic screening that includes the ascending aorta.  If good visualization of the ascending aorta cannot be achieved with echocardiogram, consider CT or MRI.

When should children be screened?

We are not sure what the best age is to start imaging young children.  In very rare cases, children have had aortic dissection as young as 12 years old; therefore we recommend a baseline imaging by echocardiogram for children when the child can sit still.  Echocardiogram is usually sufficient to see the ascending aorta and aortic arch in young children.

We are willing to help you find out what screening you should have.  Please CONTACT US.  However, we do not provide primary medical care or primary genetic counseling.  We will provide advice based on families that we have seen in our own clinic to be provided to your physician, geneticist, or cardiologist or we can help you get in touch with the correct doctors or genetics professionals in your area.

What happens when an aneurysm is found?

Early detection is the key.  Aneurysms involving the ascending aorta that are detected early can be monitored and medical therapy initiated.  Eventually the aneurysm needs to be surgically repaired to prevent life-threatening events such as an acute aortic dissection or rupture of the aorta.  If caught early, the life expectancy of someone with a thoracic aortic aneurysm should approach that of the general population.

Your cardiologists and cardiovascular surgeon will determine the optimal treatment of your aortic aneurysms.

I have a family history of aortic dissections and I want to get involved.  What can I do?

Please visit our research page to read about our research studies.  You can download our research study brochure here

In addition, a gift to the JRRP helps make it possible for the dedicated staff to accelerate their research into the genetic causes of the thoracic aortic diseases.

 


 

 

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