Expert Reviewed By: Dr. Brandon Colby MD
Aortic aneurysm, familial thoracic, TGFB2 related, is a rare but potentially life-threatening condition that affects the large blood vessel called the aorta. The aorta is responsible for carrying blood from the heart to the rest of the body. In this condition, the aortic wall weakens, leading to an enlargement or bulge known as an aneurysm. If left untreated, the aneurysm can rupture, causing severe internal bleeding and possibly death.
Recent studies have shed light on the genetic factors contributing to this condition, particularly the role of the TGFB2 gene. Understanding these genetic factors can help in diagnosing and managing the disease more effectively. Genetic testing has emerged as a valuable tool in this process, offering insights into the underlying causes and potential treatments for familial thoracic aortic aneurysm.
Understanding the Genetic Factors of Familial Thoracic Aortic Aneurysm
Research has shown that genetic factors play a significant role in the development of thoracic aortic aneurysm and dissection (TAAD) in both familial and sporadic cases. Two recent studies conducted in East and South China have expanded our understanding of the genetic contribution to this condition (1, 2). These studies found that patients with a younger age at diagnosis or normotension were more likely to carry a pathogenic/likely pathogenic variant, suggesting that routine genetic testing may lead to better prognosis.
One of the key genes implicated in familial thoracic aortic aneurysm is TGFB2. This gene encodes a protein called transforming growth factor-beta 2, which plays a crucial role in regulating cell growth, division, and differentiation. Mutations in the TGFB2 gene can lead to abnormalities in the aortic wall, increasing the risk of aneurysm formation and dissection.
Using Genetic Testing to Diagnose and Manage Familial Thoracic Aortic Aneurysm
The Role of Genetic Testing in Diagnosis
Genetic testing can help identify individuals at risk of developing familial thoracic aortic aneurysm by detecting mutations in the TGFB2 gene and other related genes. Early diagnosis is crucial in managing this condition, as it allows for timely intervention to prevent complications such as aortic dissection or rupture.
Genetic Testing for Prognosis
As mentioned earlier, studies have found that individuals with a younger age at diagnosis or normotension are more likely to carry a pathogenic/likely pathogenic variant (1, 2). Genetic testing can help identify these high-risk individuals, allowing for closer monitoring and more aggressive treatment to improve their prognosis.
Guiding Treatment Decisions
Genetic testing can also provide valuable information to guide treatment decisions for familial thoracic aortic aneurysm. For example, a study on mice with a Myh11 K1256del mutation found that impairment of Ca2+ influx predisposes the aorta to dissection (3). Identifying such genetic factors in patients can help tailor treatment strategies to address the specific underlying causes of the condition.
Identifying At-Risk Family Members
Since familial thoracic aortic aneurysm is a hereditary condition, genetic testing can help identify at-risk family members who may also carry the TGFB2 mutation or other related gene mutations. This can enable early intervention and monitoring, potentially preventing the development of life-threatening complications.
Future Directions in Familial Thoracic Aortic Aneurysm Research
As our understanding of the genetic factors contributing to familial thoracic aortic aneurysm continues to grow, there is still much to learn. A study on the 100,000 Genomes Project aimed to define FTAAD cohorts and assess the current diagnostic yield and space for future discovery (4). By uncovering new genetic factors and refining our understanding of the role of TGFB2 and other genes, we can continue to improve diagnosis, treatment, and prognosis for individuals affected by this rare but serious condition.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)