Acute Stanford type B aortic dissection-who benefits from genetic testing?

Area of Science:

• Cardiovascular Genetics
• Aortic Diseases
• Genomic Medicine

Background:

• Stanford type B aortic dissection is a rare, life-threatening condition with known genetic and modifiable risk factors.
• Identifying genetic underpinnings is crucial for understanding disease mechanisms and inheritance patterns.
• Previous studies highlight the complexity of aortic dissection phenotypes and the need for targeted genetic analysis.

Purpose of the Study:

• To investigate the utility of targeted genetic testing in a clinical cohort of Stanford type B aortic dissection patients.
• To identify causative gene variants by selecting patients based on age of onset and family history.
• To expand the knowledge of genetic factors contributing to aortic dissection.

Main Methods:

• A single-center cohort study analyzed patients with acute Stanford type B aortic dissection from 2013 to 2018.
• Patients were selected for genetic testing based on onset ≤45 years and/or positive family history of aortic disease.
• Next-generation sequencing was employed to detect genome-wide pathogenic variants and copy number variants (CNVs) in a panel of 30 familial thoracic aortic aneurysm and dissection (TAAD) genes.

Main Results:

• Nine out of 105 patients met the selection criteria for genetic testing.
• Causal variants in FBN1 (fibrillin-1) were identified in three patients.
• A novel large CNV involving the ACTA2 (actin alpha 2) gene was found in one patient, alongside two previously unreported genetic findings.

Conclusions:

• Selecting Stanford type B aortic dissection patients based on young age and family history effectively identifies disease-causing genetic variants.
• This strategy enhances diagnostic yield in clinical settings.
• The findings contribute to understanding the genetic architecture of aortic dissection.