Genetics of Heritable Thoracic Aortic Disease

Abstract

Genetic testing plays an increasing diagnostic and prognostic role in the management of patients with heritable thoracic aortic disease (HTAD). The identification of a specific variant can establish or confirm the diagnosis of syndromic HTAD, dictate extensive evaluation of the arterial tree in HTAD with known distal vasculature involvement and justify closer follow-up and earlier surgical intervention in HTAD with high risk of dissection of minimal or normal aortic size. Evolving phenotype–genotype correlations lead us towards more precise and individualized management and treatment of patients with HTAD. In this review, we present the latest evidence regarding the role of genetics in patients with HTAD.

Fatigue in patients with syndromic heritable thoracic aortic disease: a systematic review of the literature and a qualitative study of patients’ experiences and perceptions

“…Control groups: Four papers [ 32 , 57 , 58 , 61 ] compared the results of fatigue with normative data and subgroups, three [ 7 , 56 , 65 ] with healthy controls matched for age and gender, three [ 13 , 16 , 17 ] with normative data and other diseases, six [ 31 , 52 , 53 , 64 , 68 , 70 ] only with normative data. Two prospective studies [ 71 , 73 ] included pre-/post results and normative data.…”

“…Renard et al [ 6 ] found that approximately 53 candidate genes were associated with HTADs, but only 11 genes ( COL3A1, FBN1, SMAD3, TGFB2, TGFBR1, TGFBR2, ACTA2, MYH11 , MYLK, LOX and PRKG1 ) were identified as “HTAD” genes as they were assessed as having a “definitive” and “strong” gene-disease association during the curation process [ 6 ]. Mutations in the five last genes described above are known as non-syndromic HTAD (nsHTAD), as they are associated with vascular manifestation alone [ 2 , 6 , 7 ]. Mutations in the six first genes are known to cause syndromic HTAD (sHTAD), with systemic manifestations and genetic phenotype, including cardiovascular, musculoskeletal, craniofacial and ocular systems, and cutaneous features [ 4 , 5 ].…”

“…Mutations in the six first genes are known to cause syndromic HTAD (sHTAD), with systemic manifestations and genetic phenotype, including cardiovascular, musculoskeletal, craniofacial and ocular systems, and cutaneous features [ 4 , 5 ]. The most common diseases of sHTAD are Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS) and vascular Ehlers-Danlos syndrome (vEDS) [ 2 , 4 , 7 ]. The focus of the present study is sHTAD.…”

The NGS panel for genetic testing in cardiology: from the evaluation of disease risk to pharmacogenetics

“…Упущение генетического диагноза приводит к несвоевременной диагностике начального проявления аневризмы -дилатации, которая начинается при значительно меньших размерах, чем в популяции. Более того в семейных случаях заболевания также существует риск диссекции аорты даже без формирования первичной аневризмы [24,25]. Необходимость генетического тестирования, в том числе в семье, обусловлена тем, что тревожные симптомы до острого поражения аорты, как правило, появляются только у 5 % пациентов [24,25].…”

“…Более того в семейных случаях заболевания также существует риск диссекции аорты даже без формирования первичной аневризмы [24,25]. Необходимость генетического тестирования, в том числе в семье, обусловлена тем, что тревожные симптомы до острого поражения аорты, как правило, появляются только у 5 % пациентов [24,25].…”