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Page 2 of 15 Levy et al. Vessel Plus 2024;8:4 https://dx.doi.org/10.20517/2574-1209.2023.55

INTRODUCTION
Thoracic aortic dissection is a feared, highly lethal condition that can occur sporadically or with a heritable
presentation. Pre-hospital mortality can reach up to 61%, and approximately 50% of patients do not survive
past 30 days of the index event . Dissection and rupture are secondary to aneurysmal dilation of the
[1,2]
thoracic aorta and are largely preventable with prophylactic thoracic aneurysm repair. While emergent
[3]
perioperative repair mortality is approximately 20% , perioperative mortality risk for elective repair is 3% .
[4]
The challenge herein is identifying those with asymptomatic aneurysms for elective repair. The most
important risk factor for the development of thoracic aneurysm and dissection (TAAD) is a positive family
history. Aortic aneurysms can be genetically triggered (hereditary) or sporadic (no clear genetic or familial
cause). Hereditary TAAD is categorized as syndromic or non-syndromic. Syndromic aneurysms are
associated with Mendelian inheritance patterns of known genetic mutations and a pathognomonic
constellation of extra-thoracic features. Non-syndromic TAAD (ns-TAAD) may display a familial pattern,
but their genetic mutations do not follow classic Mendelian inheritance patterns, nor do patients exhibit
characteristic extra-thoracic features, which makes ns-TAAD significantly harder to recognize, especially if
surveillance and follow-up within families are limited. Thoracic aortic aneurysms are typically clinically
silent, and many are diagnosed either as incidental findings on imaging studies obtained for other reasons
or when they develop into an acute aortic dissection. Specific guidelines for intervention in ns-TAAD are
largely inferred from established syndromic TAAD and general population guidelines and are not yet
[5,6]
nuanced to the spectrum of ns-TAAD genotypes and phenotypes . To successfully evolve treatment
paradigms, further quantification of heritability risk and a more thorough understanding of the details of
genetic predisposition for ns-TAAD are needed. This article will review the current knowledge of the
genetics of aortic disease, review management guidelines, and identify research opportunities around
familial risk stratification in ns-TAAD.

METHODS
We conducted a literature search using PubMed and Ovid search engines and applied no limitations on the
date of publication. The included articles were published from 1996 to May 2023. Search terms used were
thoracic aortic AND (aneurysm OR dissection), familial thoracic aortic AND (aneurysm OR dissection),
non-syndromic thoracic AND (aneurysm OR dissection), hereditary thoracic aortic AND (aneurysm OR
dissection), hereditary OR genetic AND (thoracic aortopathy), family AND (screening OR history) AND
(thoracic aortic dissection OR thoracic aortic aneurysm), autopsy OR postmortem AND (thoracic aortic
dissection OR thoracic aortic aneurysm), risk factor AND aortic AND (aneurysm OR dissection), aortic
AND (aneurysm OR dissection) AND (sporadic OR familial), bicuspid AND aortic valve AND (aneurysm
OR dissection), familial OR genetic (AND bicuspid aortic valve). Only publications in the English language
were reviewed. Published guidelines from the American College of Cardiology Foundation/American Heart
Association, Society of Thoracic Surgeons, American Association for Thoracic Surgery, European Society of
Cardiology, and Canadian Cardiovascular Society were reviewed. Additionally, a manual search of
references from publications was conducted. From these references, we chose pertinent topics: novel genes
identified in the development of ns-TAAD, comparison of mortality risks between syndromic and ns-
TAAD, histopathology of thoracic aortopathy, genetics of bicuspid aortic valve, and an expert consensus
statement of screening guidelines.

RESULTS
Inheritance patterns
There are two types of hereditary thoracic aortopathies: syndromic and non-syndromic. Syndromic thoracic
aortopathies, including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and vascular Ehlers-Danlos
syndrome (vEDS), are associated with extra-thoracic connective tissue defects and are beyond the scope of