Molecular, genetic, and pharmacogenomic biomarkers of Type B aortic dissection risk in Marfan syndrome: a scoping review
- 1Department of Biomedical Education, California Health Sciences University College of Osteopathic Medicine
Abstract
Background: Marfan syndrome is an autosomal dominant connective tissue disorder caused primarily by pathogenic FBN1 variants, with aortic dissection a leading cause of mortality. Improved surgical thresholds have reduced Type A dissection mortality, but Type B dissection remains poorly predicted. This review maps current human evidence on molecular, genetic, and pharmacogenomic biomarkers for Type B aortic dissection risk stratification in Marfan syndrome and identifies gaps that inform a future research agenda.
Methods: A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and the framework of Arksey and O'Malley. PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library were searched for articles published between January 2010 and October 2025. Two reviewers independently screened records, extracted data, and scored each study for evidence certainty across six domains.
Results: Twenty-four studies met criteria, derived from 14 independent source populations; eight came from a single Dutch cohort network. Only two studies reported Type B dissection as a specified outcome; the remainder addressed dissection of unspecified type, aortic diameter or growth, or mechanistic endpoints. Four thematic evidence streams emerged. TGF-β pathway biomarkers show associations with aortic phenotype and disease severity across several cohorts, but their value for prospective prediction of Type B dissection remains unvalidated. Variants in TGFBR2 and TGFB2 , and FBN1 cysteine-loss variants, are associated with severe aortic phenotypes yet are not integrated into the Ghent nosology. Losartan shows heterogeneous efficacy, and a predefined randomized trial substudy suggests that benefit may depend on FBN1 variant class, although no trial has stratified outcomes by dissection type. No tool exists to stratify Type B risk in the 5 to 10 percent of clinically diagnosed patients without an identifiable FBN1 variant. Evidence certainty was moderate for the pharmacologic stream and low to very low for the other three, and the biomarker evidence is associational rather than causal.
Conclusions: A competing-risks multimodal model integrating imaging, genotype, and treatment-adjusted biomarker trajectory, developed and externally validated in multicentre prospective cohorts, represents the next research frontier.
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BibTeX
@article{essukhun2026molecular,
title = {{Molecular, genetic, and pharmacogenomic biomarkers of Type B aortic dissection risk in Marfan syndrome: a scoping review}},
author = {Amar Essukhun and Sherese Richards},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = nov,
doi = {10.3389/fcvm.2026.1975742},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1975742/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular, genetic, and pharmacogenomic biomarkers of Type B aortic dissection risk in Marfan syndrome: a scoping review
AU - Amar Essukhun
AU - Sherese Richards
PY - 2026
DA - 2026/11/04
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1975742
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1975742/full
AB - Background: Marfan syndrome is an autosomal dominant connective tissue disorder caused primarily by pathogenic FBN1 variants, with aortic dissection a leading cause of mortality. Improved surgical thresholds have reduced Type A dissection mortality, but Type B dissection remains poorly predicted. This review maps current human evidence on molecular, genetic, and pharmacogenomic biomarkers for Type B aortic dissection risk stratification in Marfan syndrome and identifies gaps that inform a future research agenda. Methods: A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and the framework of Arksey and O'Malley. PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library were searched for articles published between January 2010 and October 2025. Two reviewers independently screened records, extracted data, and scored each study for evidence certainty across six domains. Results: Twenty-four studies met criteria, derived from 14 independent source populations; eight came from a single Dutch cohort network. Only two studies reported Type B dissection as a specified outcome; the remainder addressed dissection of unspecified type, aortic diameter or growth, or mechanistic endpoints. Four thematic evidence streams emerged. TGF-β pathway biomarkers show associations with aortic phenotype and disease severity across several cohorts, but their value for prospective prediction of Type B dissection remains unvalidated. Variants in TGFBR2 and TGFB2 , and FBN1 cysteine-loss variants, are associated with severe aortic phenotypes yet are not integrated into the Ghent nosology. Losartan shows heterogeneous efficacy, and a predefined randomized trial substudy suggests that benefit may depend on FBN1 variant class, although no trial has stratified outcomes by dissection type. No tool exists to stratify Type B risk in the 5 to 10 percent of clinically diagnosed patients without an identifiable FBN1 variant. Evidence certainty was moderate for the pharmacologic stream and low to very low for the other three, and the biomarker evidence is associational rather than causal. Conclusions: A competing-risks multimodal model integrating imaging, genotype, and treatment-adjusted biomarker trajectory, developed and externally validated in multicentre prospective cohorts, represents the next research frontier.
SN - 2297-055X
ER -