Aortic dilation, genetic testing, and associated diagnoses

Zárate, Yuri A.; Sellars, Elizabeth A.; Lepard, Tiffany; Tang, Xinyu; Collins, R. Thomas

doi:10.1038/gim.2015.88

Cited by 5 publications

(7 citation statements)

References 40 publications

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“…Most genetic causes of heritable TAA disorders are inherited as monogenic defects with an autosomal dominant pattern of inheritance with high penetrance 7. Altogether, genetic triggers account for about 20% of thoracic aortic disease; however, this is likely an underestimate due to underdiagnosis of silent TAAs in family members of probands and infrequent use of genetic testing in the clinical setting 1,8,10. This review is not a comprehensive catalogue of all known genetic TAA disorders but rather offers an overview of 4 important entities: MFS, LDS, vEDS, and FTAAD (Table 1).…”

Section: Genetic Thoracic Aortic Aneurysmsmentioning

confidence: 99%

“…The bedrock of any clinical diagnosis remains obtaining a complete medical history and a detailed family history and performing a comprehensive physical exam. However, this bedrock is undermined by the variable expression, incomplete penetrance, phenotypic overlap, and clinically silent albeit life-threatening features of the genetic aortopathies 7,8. Only 5% of TAAs are symptomatic 1.…”

Section: Management Of Thoracic Aortic Aneurysmsmentioning

confidence: 99%

“…7 Altogether, genetic triggers account for about 20% of thoracic aortic disease; however, this is likely an underestimate due to underdiagnosis of silent TAAs in family members of probands and infrequent use of genetic testing in the clinical setting. 1,8,10 This review is not a comprehensive catalogue of all known genetic TAA disorders but rather offers an overview of 4 important entities: MFS, LDS, vEDS, and FTAAD (Table 1). Awareness of the more common genetic TAA disorders is paramount due to variable natural progression, different surveillance and management, and excessive early mortality.…”

Section: Genetic Thoracic Aortic Aneurysmsmentioning

confidence: 99%

“…In contrast, thoracic aortic aneurysms occur in all age groups and are more likely to be associated with a genetic background, presenting as either part of a syndromic disorder or an isolated aberration 2,7. In addition, TAAs may occur as a sporadic phenomenon or as a familial disorder; the latter may follow classic Mendelian inheritance or nonclassic inheritance of a complex trait 2,8. Elefteriades et al1 classified aortic aneurysms by their anatomic relationship to the ligamentum arteriosum.…”

Section: Introductionmentioning

confidence: 99%

“…2,7 In addition, TAAs may occur as a sporadic phenomenon or as a familial disorder; the latter may follow classic Mendelian inheritance or nonclassic inheritance of a complex trait. 2,8 Elefteriades et al 1 classified aortic aneurysms by their anatomic relationship to the ligamentum arteriosum. Aneurysms proximal to the ligament are more likely to be nonarteriosclerotic, whereas those distal to the ligamentum are primarily of arteriosclerotic origin.…”

Section: Introductionmentioning

confidence: 99%

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The Genetics of Aortopathies in Clinical Cardiology

Goyal

Keramati

Czarny

et al. 2017

Clin Med Insights Cardiol

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Aortopathies pose a significant healthcare burden due to excess early mortality, increasing incidence, and underdiagnosis. Understanding the underlying genetic causes, early diagnosis, timely surveillance, prophylactic repair, and family screening are keys to addressing these diseases. Next-generation sequencing continues to expand our understanding of the genetic causes of heritable aortopathies, rapidly clarifying their underlying molecular pathophysiology and suggesting new potential therapeutic targets. This review will summarize the pathogenetic mechanisms and management of heritable genetic aortopathies with attention to specific forms of both syndromic and nonsyndromic disorders, including Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and familial thoracic aortic aneurysm and dissection.

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Section: Genetic Thoracic Aortic Aneurysmsmentioning

confidence: 99%

Section: Management Of Thoracic Aortic Aneurysmsmentioning

confidence: 99%

Section: Genetic Thoracic Aortic Aneurysmsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Genetics of Aortopathies in Clinical Cardiology

Goyal

Keramati

Czarny

et al. 2017

Clin Med Insights Cardiol

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Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome

Bitarafan

Razmara

Khodaeian³

et al. 2020

Molec Gen & Gen Med

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Background Marfan syndrome (MFS) is a multi‐systemic autosomal dominant disease of the connective tissue characterized by the early development of thoracic aneurysms/dissections, along with various manifestations of the ocular and skeletal systems. Due to the genetic and clinical heterogeneity, the clinical diagnosis of this disorder is challenging. Loss‐of‐function mutations in FBN1 (encodes fibrillin‐1) lead to MFS type 1. Also, similar mutations in transforming growth factor β receptor 2 ( TGFBR2) gene cause MFS type 2. Both proteins involve in TGF‐β signaling. Methods In this study, genetic screening using a panel involving 14 genes, especially FBN1 and TGFBR2 , were performed on seven representatives affected members of seven unrelated Iranian families suspected with MFS. To confirm the variants, Sanger sequencing was applied to other affected/unaffected members of the families. Results A total of 13 patients showed MFS manifestations. Using genetic screening, two novel and three previously reported variants in FBN1 were identified. We also detected two variants (a novel and a previously reported variant) in the TGFBR2 gene. Conclusion In this study, we introduce three novel variants identified through gene screening in seven Iranian MFS families. This report is expected to considerably improve genetic counseling for Iranian MFS families. Early precise molecular diagnosis can be helpful for better management and improving the life expectancy of these patients.

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