Pathogenetic Basis of Aortopathy and Aortic Valve Disease

The main purpose of this study is to define the complex genetic and pathogenic basis of thoracic aortic aneurysm (TAA) and other forms of aortopathy and/or aortic valve disease by identifying novel disease-causing genes and by identifying important genetic modifiers for aortic and aortic valve disease severity.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Aortopathies Abnormalities, Multiple Acute Aortic Syndrome Aneurysm Aneurysm, Ascending Aorta Aortic Aneurysm Aortic Aneurysm, Familial Thoracic 1 Aortic Aneurysm, Giant Congenital Aortic Aneurysm, Thoracic Aortic Diseases Aortic Dissection Aortic Valve Disease Arterial Tortuosity Syndrome Ascending Aortic Aneurysm Ascending Aortic Disease Autosomal Recessive Cutis Laxa Bicuspid Aortic Valve Bicuspid Aortic Valve Disease Bicuspid Aortic Valve-Associated Aortopathy Bone Diseases Bone Diseases, Developmental Cardiovascular Abnormalities Cardiovascular Diseases Chromosome Disorders Collagen Diseases Congenital Abnormalities Congenital Contractural Arachnodactyly Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Craniofacial Abnormalities Cutis Laxa, Autosomal Recessive, Type I Descending Aortic Aneurysm Descending Aortic Disease Disorders of Sex Development Dissection, Blood Vessel Dissection, Thoracic Aorta Ehlers-Danlos Syndrome Ehlers-Danlos Syndrome, Type IV Endocrine System Diseases Familial Thoracic Aortic Aneurysm and Aortic Dissection Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Gonadal Disorders Gonadal Dysgenesis Heart Defects, Congenital Heart Diseases Heart Valve Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Loeys-Dietz Syndrome Male Urogenital Diseases Marfan Syndrome Musculoskeletal Abnormalities Musculoskeletal Diseases PHACE Syndrome Sex Chromosome Disorders Sex Chromosome Disorders of Sex Development Shprintzen Golberg craniosynostosis Shprintzen-Goldberg Syndrome Skin Abnormalities Skin Diseases Skin Diseases, Genetic Skin and Connective Tissue Diseases Thoracic Aortic Aneurysm Thoracic Aortic Disease Thoracic Aortic Dissection Thoracic Aortic Rupture Turner Syndrome Urogenital Abnormalities Urogenital Diseases Vascular Diseases Vascular Ehlers-Danlos Syndrome

Sex eligibility

All sexes

Study type

Observational

Primary location

Childrens Healthcare of Atlanta, Atlanta, Georgia, United States

About this study

Thoracic aortic aneurysm (TAA) is a type of aortopathy describing dilation of the proximal aortic dimensions including the aortic root, which is a risk factor for aortic dissection and sudden cardiac death. TAA and other forms of aortopathy (e.g. aortic tortuosity or aortic hypoplasia/stenosis) develop in the presence or absence of additional cardiovascular malformations including bicuspid aortic valve. TAA is associated with connective tissue disorders (e.g. Marfan syndrome), and familial clustering has been identified in a significant proportion of nonsyndromic cases, establishing high heritability. Pedigree analysis of TAA kindreds clearly identifies complex inheritance; however, progress towards understanding the genetic basis of TAA and other forms of aortopathy and, ultimately, the susceptibility to aortic dissection remains incomplete. There is a clinical need to develop novel methods for predicting disease risk based on genotype and phenotype, to further elucidate the genetic and pathogenic mechanisms of aortopathy, and to improve medical and surgical therapies. The overarching hypothesis of this study is that individual genetic variation modulates susceptibility to disease severity and progression. The goals of this study are 1) to ascertain a cohort of subjects who have aortopathy and/or aortic valve disease including TAA or who have genetic risk for the development of aortopathy and/or aortic valve disease, 2) to collect paired blood and tissue samples from well-characterized subjects, family members of subjects, and controls to perform genome-wide DNA sequence, histopathologic, transcriptional, and proteomic analyses, and 3) to establish a tissue biorepository with detailed phenotype information to facilitate a broad spectrum of current and future studies.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Open to external enrollment:

Subjects with a genetic diagnosis of Marfan Syndrome (MDS), Loeys-Dietz Syndrome (LDS), or Vascular Ehlers-Danlos Syndrome (EDS); (Positive genetic testing or a previous cardiac study required to be eligible)
Family members of eligible subjects (Only family members of subjects with syndromic diagnoses are eligible for external enrollment at this time)
Closed to external enrollment:

Subjects with aortic disease including TAA* or dissection, aortic tortuosity, or aortic hypoplasia/stenosis (based on any cardiac imaging modality including echocardiography, CT, MRI, or angiography)
Subjects with aortic valve disease (bicuspid, unicuspid, or tricuspid disease)
Control subjects having tissue removed during a surgical procedure (e.g. coronary artery bypass graft surgery (CABG), cardiac transplant, etc.)

Exclusion criteria

Inability or unwillingness to provide consent (assent when indicated)

Treatment and study plan

Primary outcomes

Biorepository Establishment

Time frame: 20 years

Establish a biorepository with detailed phenotype information to facilitate a broad spectrum of current and future studies
Genetic Analysis

Time frame: 20 years

The mechanisms of TAA pathogenesis will be determined by studying explanted aortic tissue and cells derived from patients with TAA for gene expression, protein expression, and other functional assays.

Sponsors and collaborators

Lead sponsor

Yale University

Other

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Acronym: TAA

Important dates

Study start: 2015
Primary completion: 2030
Study completion: 2030
First posted: Feb 22, 2018
Registry last updated: Feb 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed