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Pathophysiology and Pathogenesis of Marfan Syndrome

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Progress in Heritable Soft Connective Tissue Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1348))

Abstract

Marfan syndrome (MFS) is a systemic connective tissue disorder that is inherited in an autosomal dominant pattern with variable penetrance. While clinically this disease manifests in many different ways, the most life-threatening manifestations are related to cardiovascular complications including mitral valve prolapse, aortic insufficiency, dilatation of the aortic root, and aortic dissection. In the past 30 years, research efforts have not only identified the genetic locus responsible but have begun to elucidate the molecular pathogenesis underlying this disorder, allowing for the development of seemingly rational therapeutic strategies for treating affected individuals. In spite of these advancements, the cardiovascular complications still remain as the most life-threatening clinical manifestations. The present chapter will focus on the pathophysiology and clinical treatment of Marfan syndrome, providing an updated overview of the recent advancements in molecular genetics research and clinical trials, with an emphasis on how this information can focus future efforts toward finding betters ways to detect, diagnose, and treat this devastating condition.

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Abbreviations

AT1R:

Ang-II type-I specific receptor

ARB:

Angiotensin receptor blocker

AIMS:

Aortic Irbesartan Marfan Study

AHT:

Arterial hypertension

cbEGF:

Calcium-binding EGF

COPD:

Chronic obstructive pulmonary disease

CVG:

Composite valved-graft

CCA:

Congenital contractural arachnodactyly

CNV:

Copy number variant

EGF:

Epidermal growth factor

ECM:

Extracellular matrix

EKR:

Extracellular signal related kinase

FBN1:

Fibrillin-1

HTAD:

Heritable thoracic aortic disease

LLC:

Large latent complex

LAP:

Latency associated peptide

LTBP:

Latent transforming growth factor binding protein

LDS:

Loeys-Dietz syndrome

MFS:

Marfan syndrome

MVPS:

Mitral valve prolapse syndrome

MAPK:

Mitogen-activated protein kinase

NGS:

Next generation sequencing

PHN:

Pediatric heart network

PEARS:

Personalized external aortic root support

PTC:

Premature termination codon

SLC:

Small latent complex

TEVAR:

Thoracic endovascular aortic repair

TGF-β:

Transforming growth factor-β

VSARR:

Valve-sparing root replacement

VUS:

Variant of unknown significance

WES:

Whole-exome sequencing

WGS:

Whole-genome sequencing

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Authors and Affiliations

  1. Division of Cardiothoracic Surgery, Department of Surgery, Medical University of South Carolina, Charleston, SC, USA

    Sanford M. Zeigler & Brandon Sloan

  2. Division of Cardiothoracic Surgery, Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA

    Jeffrey A. Jones

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  1. Sanford M. Zeigler
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  2. Brandon Sloan
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  3. Jeffrey A. Jones
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Correspondence to Jeffrey A. Jones .

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  1. Department of Pathology, College of Veterinary Medicine, and Department of Basic Sciences, AU/UGA Medical Partnership, The University of Georgia, Athens, GA, USA

    Jaroslava Halper

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Zeigler, S.M., Sloan, B., Jones, J.A. (2021). Pathophysiology and Pathogenesis of Marfan Syndrome. In: Halper, J. (eds) Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology, vol 1348. Springer, Cham. https://doi.org/10.1007/978-3-030-80614-9_8

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