Marfan Syndrome, A Review

Marfan syndrome is named after the French pediatrician Antoine Bernard-Jean Marfan who described in 1896 a girl with arachnodactyly and long limbs1. The patient also had congenital contractures of the elbows and would not fulfill the current criteria for Marfan syndrome. She probably was suffering from a condition that we now call contractural arachnodactyly, caused by mutations in the FBN2 gene.The clinical features of Marfan syndrome affect many systems of the body. The most obvious are the skeletal features, long limbs, tall stature, long thin fingers (arachnodactyly or spider fingers). The skeletal features can be scored objectively as: arm span more than 1.05 x body length; wrist sign (thumb and index finger can encircle the wrist of the other hand with at least one digit overlap) and thumb sign (when making a fist around the thumb, one digit of the thumb sticks out). The main neurological symptom is dural ectasias. The most severe symptoms are cardiovascular: mitralis valve prolapse, aortic dilatation and thoracic aortic aneurysms and dissections, which may lead to sudden death5. However, I noticed in discussions with patients that they often consider the ocular symptoms, severe myopia and lens luxation, the worst for themselves, because the latter may lead to blindness.

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Glutathione system participation in thoracic aneurysms from patients with Marfan syndrome

VASA ◽

10.1024/0301-1526/a000609 ◽

2017 ◽

Vol 46 (3) ◽

pp. 177-186 ◽

Cited By ~ 8

Author(s):

Alejandra María Zúñiga-Muñoz ◽

Israel Pérez-Torres ◽

Verónica Guarner-Lans ◽

Elías Núñez-Garrido ◽

Rodrigo Velázquez Espejel ◽

...

Keyword(s):

Aortic Aneurysm ◽

Marfan Syndrome ◽

Aortic Aneurysms ◽

Aortic Dilatation ◽

Glutathione S Transferase ◽

Reduced And Oxidized Glutathione ◽

Total Antioxidant ◽

Elevated Activity ◽

Acute Dissection ◽

Thoracic Aneurysms

Abstract. Background: Aortic dilatation in Marfan syndrome (MFS) is progressive. It is associated with oxidative stress and endothelial dysfunction that contribute to the early acute dissection of the vessel and can result in rupture of the aorta and sudden death. We evaluated the participation of the glutathione (GSH) system, which could be involved in the mechanisms that promote the formation and progression of the aortic aneurysms in MFS patients. Patients and methods: Aortic aneurysm tissue was obtained during chest surgery from eight control subjects and 14 MFS patients. Spectrophotometrical determination of activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO) index, carbonylation, total antioxidant capacity (TAC), and concentration of reduced and oxidized glutathione (GSH and GSSG respectively), was performed in the homogenate from aortic aneurysm tissue. Results: LPO index, carbonylation, TGF-β1, and GR activity were increased in MFS patients (p < 0.04), while TAC, GSH/GSSG ratio, GPx, and GST activity were significantly decreased (p < 0.04). Conclusions: The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

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Marfan Syndrome and Related Heritable Thoracic Aortic Aneurysms and Dissections

Current Pharmaceutical Design ◽

10.2174/1381612821666150826093152 ◽

2015 ◽

Vol 21 (28) ◽

pp. 4061-4075 ◽

Cited By ~ 3

Author(s):

Julie Backer ◽

Marjolijn Renard ◽

Laurence Campens ◽

Laura Mosquera ◽

Anne Paepe ◽

...

Keyword(s):

Marfan Syndrome ◽

Aortic Aneurysms ◽

Thoracic Aortic Aneurysms

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Quantitative not qualitative histology differentiates aneurysmal from nondilated ascending aortas and reveals a net gain of medial components

Scientific Reports ◽

10.1038/s41598-021-92659-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sameh Yousef ◽

Nana Matsumoto ◽

Issam Dabe ◽

Makoto Mori ◽

Alden B. Landry ◽

...

Keyword(s):

Extracellular Matrix ◽

Quantitative Assessment ◽

Cell Number ◽

Aortic Aneurysms ◽

Aortic Dilatation ◽

Adaptive Responses ◽

Cross Sectional ◽

Thoracic Aortic Aneurysms ◽

Medial Degeneration ◽

The Media

AbstractMedial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

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Pulse Wave Velocity Involving Proximal Portions of the Aorta Correlates with the Degree of Aortic Dilatation at the Sinuses of Valsalva in Ascending Thoracic Aortic Aneurysms

Annals of Vascular Diseases ◽

10.3400/avd.oa.14-00063 ◽

2014 ◽

Vol 7 (4) ◽

pp. 404-409 ◽

Cited By ~ 2

Author(s):

Simon W Rabkin ◽

Kenneth K. Chan ◽

Bryan Chow ◽

Michael T. Janusz

Keyword(s):

Pulse Wave Velocity ◽

Wave Velocity ◽

Pulse Wave ◽

Aortic Aneurysms ◽

Aortic Dilatation ◽

Thoracic Aortic Aneurysms

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587 Role of Long Noncoding RNAs in the Pathogenesis of Thoracic Aortic Aneurysms in Marfan Syndrome

Heart Lung and Circulation ◽

10.1016/j.hlc.2020.09.594 ◽

2020 ◽

Vol 29 ◽

pp. S302

Author(s):

C. Gover ◽

S. Maleki ◽

B. Hambly ◽

P. Bannon ◽

R. Jeremy ◽

...

Keyword(s):

Marfan Syndrome ◽

Noncoding Rnas ◽

Aortic Aneurysms ◽

Long Noncoding Rnas ◽

Thoracic Aortic Aneurysms

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The spectrum of FBN1, TGFβR1, TGFβR2 and ACTA2 variants in 594 individuals with suspected Marfan Syndrome, Loeys–Dietz Syndrome or Thoracic Aortic Aneurysms and Dissections (TAAD)

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2014.03.011 ◽

2014 ◽

Vol 112 (2) ◽

pp. 171-176 ◽

Cited By ~ 29

Author(s):

Jordan P. Lerner-Ellis ◽

Saud H. Aldubayan ◽

Amy Lovelette Hernandez ◽

Melissa Allard Kelly ◽

Aaron J. Stuenkel ◽

...

Keyword(s):

Marfan Syndrome ◽

Aortic Aneurysms ◽

Thoracic Aortic Aneurysms

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Abstract 18889: Circulating microRNA Implicated in the TGF-β Signalling Pathway are Altered in Marfan Syndrome

Circulation ◽

10.1161/circ.132.suppl_3.18889 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Elizabeth N Robertson ◽

Yaxin Lu ◽

Alex Sahagian ◽

Donna Lai ◽

Murat Kekic ◽

...

Keyword(s):

Gene Expression ◽

Cardiovascular Disease ◽

Marfan Syndrome ◽

Regulation Of Gene Expression ◽

Left Ventricular ◽

Microrna Expression ◽

Aortic Aneurysms ◽

Circulating Microrna ◽

Transcriptional Level ◽

Aortic Dilatation

Thoracic aortic aneurysms in Marfan Syndrome (MFS) caused by mutations in FBN1 are associated with altered TGF-β signaling. Regulation of gene expression can occur at the level of microRNA, which can modify signaling pathways. We hypothesized that there would be altered microRNA expression in MFS that may alter the expression of signaling proteins. Total RNA was isolated from whole blood collected in PAXgene® tubes (PreAnalytiX), from 13 MFS patients with aortic dilatation (6F, 7M; Ao Diameter 44.4±6.0mm; Age 39±12yrs) and 10 normal controls (5F, 5M; Ao Diameter 32.3±5mm; Age 34±10yrs). The RNA was reverse transcribed with Human Pool A & B primers and qPCR was performed on the subsequent cDNA using TaqMan® OpenArray® Human miRNA Panels (2454 targets) (ThermoFisher). microRNA expression was considered to be significantly altered if there was >2 fold change (p<0.05) compared to controls. microRNA that were identified as significantly altered were then validated with qPCR using targeted primers on an additional 33 MFS patients (15F, 21M; Ao Diameter 44.2±5.0mm; Age 37±13yrs). In MFS patients, the OpenArray® identified 30 microRNA were significantly altered (22 up regulated, 8 down regulated). Of these, 12 were confirmed to be altered using targeted qPCR (Graph 1). Three of these have previously been identified as modifiers of the TGF-β signaling pathway (miR 17, miR 93, miR 93*). Three were from the let-7 family (let-7e, let-7f, let-7g), which are involved in terminal cell differentiation and have been implicated in several cardiovascular disease processes. Another three have been shown to be dysregulated in various cardiovascular disease states including atherosclerotic thoracic aortic aneurysm and left ventricular hypertrophy (miR 208, miR 486, miR 378). This study provides novel evidence for adaptive responses at the post-transcriptional level of gene expression that may modulate aneurysm development in Marfan syndrome.

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