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It's Scientific Sunday and Genetics 101 with Ryan Rodarmer, Director of Genetic Education

Updated: Jun 10, 2023



Today is Scientific Sunday at Aortic Hope and we are excited to continue our Genetics 101 Series with Ryan Rodarmer.


Over the next couple of weeks, Ryan will discuss a variety of topics related to genetics. Use these discussions as a way to have a conversation with your physician.


Introduction


Hello again, friends! In our previous blog posts, we talked about genetic risk factors for hereditary thoracic aortic diseases, including syndromic conditions like Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome. Today, we're going to focus on a genetic cause that isn’t part of a larger syndrome - non-syndromic hereditary thoracic aortic disease (HTAD), a condition that might be relevant to some aortic dissection survivors or those with a family history of aortic dissection. Don’t forget to check out previous blog posts if I use a term you aren’t familiar with. The posts about specific syndromes aren’t necessary, but the first post from the series really laid the groundwork for our discussion and is critical!  


As always, don't hesitate to email me at ryan@myaorticjourney.com if you have any questions. And remember... #thinkaortathinkfamily!


What is Non-Syndromic Hereditary Thoracic Aortic Disease (HTAD)?  


Like the syndromes we have discussed, non-syndromic HTAD is also a type of aortic disease that affects the thoracic aorta—the large blood vessel that carries blood from your heart to the rest of your body. You may also see it called hereditary thoracic aortic aneurysm and dissection, or HTAAD. Unlike syndromic conditions, however, non-syndromic HTAD doesn't come with additional symptoms affecting other parts of the body, like tall stature or hypermobility or eye problems. However, it is inherited in the same manner as Marfan syndrome or vascular EDS, which we will discuss further below.


Although relatively rare, non-syndromic HTAD is an important condition to understand, as it can lead to life-threatening complications, such as aortic dissection and rupture, just like the syndromic genetic conditions previously discussed.  


Genetics of Non-Syndromic HTAD  


Non-syndromic HTAD is caused by changes (mutations) in certain genes. Just like syndromic conditions, non-syndromic HTAD is typically inherited in an autosomal dominant manner, which means that you only need to inherit one copy of the mutated gene from one parent to have the condition. It’s passed down in a 50/50-type manner. It could also occur as the result of a new genetic mutation, just as we have discussed for the other conditions.


Some common genes associated with non-syndromic HTAD include ACTA2, MYH11, MYLK, and PRKG1. Interestingly, mutations in genes we have already discussed related to known syndromes are now known to be capable of causing non-syndromic aortic disease as well - like TGFBR1, TGFBR2, SMAD3, TGFB2, and FBN1. Genetic testing and increased awareness are presenting us with lots of new knowledge – and we have A LOT left to figure out, but there’s constant progress being made.


On that note – those who meet the diagnostic criteria below may need to temper their expectations on genetic testing. It’s great when we can find the genetic mutation responsible – gives us insight into how to manage the

disease, from imaging/surveillance type and frequency, to when one should consider surgery to prevent dissection, to helping to identify which family member have inherited the risk and which have not. However, in HTAD, the chance of finding the mutation responsible is still quite low – like 20% or so. This is because we haven’t discovered all of the genetic causes yet. Just because genetic testing is negative, it doesn’t mean it’s not genetic. I wrote a helpful article on that for the Ritter Foundation – check it out here.


Symptoms and Diagnosis


Non-syndromic HTAD can be difficult to detect because it often doesn't cause any symptoms until complications arise. We don’t have clues on the outside to a possible problem on the inside – there aren’t certain characteristics that could be spotted by a knowledgeable physician – so our biggest tool is family history. Personally, I am fortunate that my aneurysm was incidentally found as the result of a (completely unrelated) heart infection. There was no known family history – I was the “proband,” which means the first family member identified. So without family history and without prior knowledge of my aneurysm, I may have handled the pain I experienced at dissection differently – I may have decided to wait it out as opposed to immediately calling 911 and advocating for immediate CT imaging.


It took a while to get family members checked – they finally took the risk seriously when I dissected – but we now know that my father and his two sisters also have aortic disease. So in my case, even though there WAS a family history, nobody came to medical attention except for me, and kind of by accident. We would have never known. So non-syndromic HTAD can be very tricky, and unfortunately the first clue of its presence in a family is often aortic dissection.


We don’t need to spend a lot of time here, because this is covered in great detail elsewhere – but what is it like to dissect? Some people might experience:  


  • · Pain in the chest, back, or neck – usually sudden, and extreme – far different than heart attack pain... some describe tearing/ripping sensations, but mine was more like blunt, constant pressure

  • · Shortness of breath  


To diagnose non-syndromic HTAD, doctors typically use imaging techniques like CT scans, MRIs, or echocardiograms, and combine that with family history information and/or genetic testing. Not everyone with thoracic aortic disease meets the criteria for HTAD; however, as I previously mentioned, when the aortic root (where the aorta connects to the heart) or the ascending aorta are enlarged, it is largely thought to have at least some genetic cause/influence - even if genetic testing can’t find the culprit. And that’s where surveillance for family members via echocardiogram, CT, etc. comes in. More on that below.


Diagnostic Criteria for HTAD  


Given the importance of early detection for at-risk family, it's crucial to understand the diagnostic criteria for hereditary thoracic aortic aneurysm and dissection (HTAD):  


  • · Thoracic aortic dissection or aneurysm in addition to the following:

  • •The absence of other syndromic features (such as those seen in Marfan syndrome, Loeys-Dietz syndrome, or vascular Ehlers-Danlos syndrome)  


Without family history, HTAD is highly suspected when thoracic aortic aneurysm/dissection is present at less than age 60.  


Risk Factors and Complications  


The main risk factor is obviously family history and genetics. However, just as for aortic aneurysm in general, there are several factors that can increase the risk of developing thoracic aortic disease which should 100% be avoided in those with a genetic predisposition/family history of aortic disease. These include:


  • · Hypertension (high blood pressure)  

  • · Smoking  


Treatment and Management  


Treatment for non-syndromic HTAD focuses on managing risk factors and preventing complications.  


Medical Management  


Blood pressure control: Keeping blood pressure in check is crucial for reducing stress on the aortic wall and preventing dissections.  


Medications: Doctors may prescribe beta-blockers or other medications to help manage blood pressure and reduce the risk of complications.  


Surgical Intervention  


In some cases, surgery may be necessary to repair or replace the affected part of the aorta. Indications for surgery include:  


  • · A rapidly expanding aortic aneurysm  

  • · A high risk of aortic dissection or rupture, based on the gene mutation or size of the aneurysm


There are different types of surgery, such as aortic root replacement and valve-sparing aortic root replacement, which your doctor will discuss with you based on your individual circumstances.  


Lifestyle Modifications  


  • · Regular exercise: Staying active can help maintain a healthy weight and manage blood pressure.  

  • · Healthy diet: Eating a balanced diet can also help manage blood pressure and overall heart health.  

  • · Stress management: Reducing stress can help control blood pressure and lower the risk of aortic complications.  


Prognosis and Prevention  


With early detection and appropriate management, the long-term outlook for non-syndromic HTAD patients can be positive. Preventive measures for at-risk individuals include:  

  • · Genetic counseling and testing: This can help determine your risk of inheriting non-syndromic HTAD and guide medical management.  

  • · Regular medical check-ups, regular surveillance via imaging: Staying on top of your health with routine check-ups and screenings can help catch any issues early.  

  • · Monitoring for symptoms: Be vigilant for any signs or symptoms of non-syndromic HTAD and report them to your doctor promptly.  


Conclusion  


Non-syndromic hereditary thoracic aortic disease is a complex condition that requires a comprehensive understanding of its genetic basis, diagnostic criteria, and management strategies. By staying informed and proactive in your care, you can help prevent complications and improve your overall quality of life.  


Remember, you are not alone in this journey. Reach out to others in similar situations, share your experiences, and continue to raise awareness about non-syndromic HTAD. Together, we can support each other and make a difference.


If you have any questions or concerns, please feel free to reach out to me at ryan@myaorticjourney.com. Let's continue learning and supporting one another on this journey with the help of Aortic Hope. Remember, #thinkaortathinkfamily!

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