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Familial thoracic aortic aneurysm and dissection
Also known as Familial thoracic aortic aneurysm (ACTA2) · Familial thoracic aortic aneurysm (SMAD3) · Familial thoracic aortic aneurysm (TGFBR2) · FTAAD
FTAAD increases the risk of the aorta bulging (aneurysm) or tearing (dissection), which can be life-threatening. This condition often runs in families and is caused by specific changes in certain genes.
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Overview
Familial Thoracic Aortic Aneurysm and Dissection (FTAAD) is a group of inherited disorders that primarily affect the aorta, the largest artery in the body. The aorta carries oxygen-rich blood from the heart to the rest of the body. In FTAAD, the walls of the thoracic aorta - the part of the aorta in the chest - can weaken over time. This weakening can lead to two main problems: an aneurysm, which is a balloon-like bulge, or a dissection, which is a tear in the inner layer of the aortic wall [PMID:33678566].
These aortic abnormalities can be very serious. Aortic dissection is a medical emergency requiring immediate attention, as it can be life-threatening. FTAAD is considered rare, meaning it affects a relatively small number of people, but its exact prevalence is not well established. Understanding the familial nature of this condition is crucial for identifying at-risk individuals and providing appropriate care.
Symptoms & clinical features
FTAAD can often be asymptomatic, meaning individuals may not experience any symptoms until an aneurysm becomes large or a dissection occurs. When symptoms do appear, they depend on whether an aneurysm or dissection is present, and where it is located.
Symptoms of an aortic aneurysm can include chest pain, back pain, hoarseness, difficulty swallowing, or shortness of breath. These symptoms arise as the enlarging aorta presses on nearby structures. An acute aortic dissection, however, typically presents with sudden, severe chest or back pain, often described as a tearing or ripping sensation. Other symptoms can include sweating, nausea, weakness, or feeling faint. Early recognition of these symptoms is vital for prompt medical intervention.
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Affected organs
The primary organ affected in FTAAD is the aorta, specifically the thoracic portion located in the chest. This includes the ascending aorta (rising from the heart), the aortic arch (curving over the heart), and the descending thoracic aorta. The weakening of the aortic wall can also sometimes extend to other arteries, such as those supplying the brain or limbs, though this is less common than the primary aortic involvement.
While the main impact is on the cardiovascular system, some of the genes associated with FTAAD can also have broader effects. For instance, certain genetic changes might lead to subtle features affecting other connective tissues, though these are typically less pronounced than the aortic issues.
Risks & severity
The severity of FTAAD can vary significantly among affected individuals, even within the same family. The main risks associated with FTAAD are aortic aneurysm rupture and aortic dissection, both of which are life-threatening events. The risk of these events generally increases with the size of the aneurysm.
The age of onset for aortic events in FTAAD can vary widely, from childhood into older adulthood, though they often manifest in early to middle adulthood. Regular surveillance is key to monitoring aortic size and identifying when surgical intervention might be necessary to prevent rupture or dissection. Family history can help predict individual risk, but each person's situation is unique.
Genetic causes
Familial Thoracic Aortic Aneurysm and Dissection (FTAAD) is caused by pathogenic variants in specific genes that play a role in maintaining the structure and function of the aortic wall. The genes most commonly associated with FTAAD in our reference dataset include *ACTA2*, *SMAD3*, and *TGFBR2* [PMID:24075908].
*ACTA2* provides instructions for making alpha-2 smooth muscle actin, a protein essential for the contractile function of smooth muscle cells. These cells are a major component of the aortic wall, providing strength and elasticity. Pathogenic variants in *ACTA2* can impair smooth muscle function, leading to a weakened aorta. *SMAD3* is involved in cell signalling pathways that regulate cell growth and differentiation. Changes in *SMAD3* can disrupt these processes, affecting the integrity of connective tissue throughout the body, including the aorta [PMID:28604724]. Lastly, *TGFBR2* encodes a protein that is part of the transforming growth factor-beta (TGF-β) signalling pathway, which is critical for cell growth, development, and tissue repair. Pathogenic variants in *TGFBR2* can lead to abnormal TGF-β signalling, contributing to connective tissue disorders and weakening of the aorta.
- ACTA2 actin alpha 2, smooth muscleThe ACTA2 gene provides instructions for producing smooth muscle alpha-2 actin, a key protein involved in the contraction of smooth muscles found in various internal organs and blood vessel walls.
- SMAD3 SMAD family member 3The SMAD3 gene provides instructions for a protein that plays a central role in the transforming growth factor-beta (TGF-β) signalling pathway, influencing cell growth, division, and movement.
- TGFBR2 transforming growth factor beta receptor 2The *TGFBR2* gene provides instructions for making a protein central to cell signalling, influencing processes such as cell growth, division, and differentiation.
Inheritance pattern
Familial Thoracic Aortic Aneurysm and Dissection (FTAAD) is typically inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of an altered gene (from either parent) to be at risk of developing the condition.
If one parent has FTAAD due to a pathogenic variant in one of these genes, there is a 50% chance with each pregnancy that their child will also inherit the altered gene and therefore be at risk. This pattern explains why the condition often runs in families. Individuals with a family history of FTAAD may be referred for genetic counselling and testing to understand their personal risk and options.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Subtypes & variants
This page covers Familial thoracic aortic aneurysm and dissection as a single condition. Several distinct variants and clinical subtypes are recognised in the literature - they share the underlying biology and broad management approach, but differ in severity, age of onset, or causative gene:
- ACTA2 ACTA2 OMIM 611788
ACTA2 is the most common single-gene cause of non-syndromic FTAAD. Highly variable age of onset; some carriers also develop premature stroke or coronary disease. Iris flocculi can be a clinical clue.
- SMAD3 (Loeys-Dietz spectrum) SMAD3 OMIM 613795
SMAD3 variants cause TAAD with widespread arterial tortuosity, often within the Loeys-Dietz spectrum. Aortic surgical thresholds are lower than for non-syndromic disease.
- TGFBR2 (Loeys-Dietz spectrum) TGFBR2 OMIM 610168
TGFBR2 variants cause Loeys-Dietz syndrome with aggressive aortic disease and dissection at smaller diameters than in Marfan syndrome. Earlier prophylactic root replacement is often indicated.
Diagnosis & testing
The diagnosis of FTAAD is typically suspected based on a personal or family history of thoracic aortic aneurysm or dissection, particularly if these events occur at a younger age or without typical risk factors like high blood pressure. Imaging studies, such as echocardiography, CT scans, or MRI scans, are used to visualise the aorta and identify any aneurysms or dissections.
Confirmation of FTAAD often involves genetic testing. If a genetic cause is suspected, individuals will typically be referred to a clinical genetics service within the NHS. Genetic testing looks for specific pathogenic variants in genes known to be associated with FTAAD, such as *ACTA2*, *SMAD3*, or *TGFBR2*. This testing can be carried out under relevant NHS Genomic Medicine Service R-codes, if clinically appropriate. A confirmed genetic diagnosis can guide management for the individual and help identify at-risk family members.
Management & lifestyle
The management of FTAAD focuses on preventing aortic dissection and rupture through regular monitoring and, if necessary, surgical intervention. Medical management often includes medications to lower blood pressure and heart rate, which can reduce stress on the aortic wall. Lifestyle modifications, such as avoiding strenuous activities that increase blood pressure, may also be recommended.
Regular surveillance imaging (e.g., CT or MRI scans) is crucial to monitor the size of the aorta. Surgical repair or replacement of the affected aortic segment is considered when an aneurysm reaches a certain size, or if it is rapidly growing. This preventive surgery aims to avert life-threatening complications. Management plans are highly individualised and developed by a multidisciplinary team of specialists, including cardiologists, cardiac surgeons, and clinical geneticists.
UK care pathway
In the UK, individuals suspected of having FTAAD typically enter the NHS Genomic Medicine Service pathway. This often begins with a referral from a cardiologist or other specialist to a clinical genetics service. Genetic counsellors play a key role in explaining the condition, inheritance patterns, and the implications of genetic testing for both the individual and their wider family.
Genetic testing for FTAAD-related genes is performed through NHS Genomic Laboratory Hubs, often using relevant R-codes for thoracic aortic aneurysm and dissection. A confirmed genetic diagnosis informs personalised management plans, including surveillance protocols and discussions about risk-reducing interventions, all within the framework of NHS clinical guidelines.
Frequently asked questions
What is the difference between an aneurysm and a dissection?
An aneurysm is a localised bulge or ballooning in the wall of a blood vessel, like a weak spot. A dissection is a tear in the inner layer of the blood vessel wall, allowing blood to flow between the layers and potentially leading to a rupture.
If someone in my family has FTAAD, should I be tested?
If a close relative has a confirmed genetic diagnosis of FTAAD, it is generally recommended to discuss your own risk with your GP or a clinical geneticist. They can advise on whether genetic testing or screening is appropriate for you.
Can FTAAD be prevented?
The underlying genetic cause of FTAAD cannot be prevented. However, careful management, including regular monitoring, blood pressure control, and sometimes preventive surgery, can significantly reduce the risk of life-threatening complications like aortic dissection or rupture.
What kind of monitoring will I need if I have FTAAD?
Monitoring for FTAAD typically involves regular imaging of your aorta, such as CT scans, MRI scans, or echocardiograms, to measure its size and check for any changes. Your doctors will decide the frequency of these scans based on your individual circumstances.
Is there a cure for FTAAD?
Currently, there is no cure for the genetic cause of FTAAD. Management focuses on preventing serious complications through surveillance and interventions, such as medications to control blood pressure or surgery to repair or replace the affected part of the aorta, ensuring long-term health.
References
- Goyal A, Keramati AR, Czarny MJ. The Genetics of Aortopathies in Clinical Cardiology. Clinical Medicine Insights. Cardiology. 2017. PMID: 28607545
- Sathananthan G, Rychel V, Yam J. A Postpartum Type A Dissection. JACC. Case reports. 2020. PMID: 34316984
- Diletta L, Enrico R, Germano M. Thoracoabdominal aortic aneurysm in connective tissue disorder patients. Indian journal of thoracic and cardiovascular surgery. 2022. PMID: 35463710
- Wang Y, Wu B, Li J. Sinus of Valsalva Aneurysm in Females. International heart journal. 2022. PMID: 36372407
- Krywanczyk A, Rodriguez ER, Tan CD. Thoracic Aortic Aneurysm and Dissection: Review and Recommendations for Evaluation. The American journal of forensic medicine and pathology. 2023. PMID: 36877084
- Cecchi AC, Boerio ML, Marin I. Preventing Acute Aortic Dissections: The Power of Familial Screening and Risk Assessment. Journal of the American Heart Association. 2022. PMID: 35383462
- Brownstein AJ, Ziganshin BA, Elefteriades JA. Human aortic aneurysm genomic dictionary: is it possible? Indian journal of thoracic and cardiovascular surgery. 2019. PMID: 33061067
- Crawford JD, Hsieh CM, Schenning RC. Genetics, Pregnancy, and Aortic Degeneration. Annals of vascular surgery. 2016. PMID: 26381327