Pathophysiology and Pathogenesis of Marfan Syndrome

Zeigler, Sanford; Sloan, Brandon; Jones, Jeffrey A.

doi:10.1007/978-3-030-80614-9_8

Cited by 53 publications

(39 citation statements)

References 107 publications

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“…In 90% of cases [ 189 ], MFS is caused by mutations in Fibrillin-1 (FBN1), located on chromosome 15q21.1 and containing 65 exons [ 190 ]. The cardinal features involve the ocular and skeletal systems (e.g., tall stature, arachnodactyly, and ectopia lentis) [ 191 ], but the most life-threatening manifestations are related to cardiovascular complications, including mitral valve prolapse, arrhythmias, coronary artery disease, left ventricular hypertrophy, congestive heart failure, aortic insufficiency, dilatation of the aortic root, and aortic dissection [ 192 , 193 ]. Considering those cardiovascular complications, early recognition and appropriate management are critical for patients with MFS.…”

Section: Pediatrics Syndromes Associated With Oxidative Stressmentioning

confidence: 99%

The Impact of Oxidative Stress on Pediatrics Syndromes

et al. 2022

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Oxidative stress is a condition determined by an imbalance between antioxidant and oxidative factors. Oxidative stress can have serious consequences on our organism. Indeed, it causes both necrosis and cell apoptosis, determining cellular aging, increased carcinogenesis, vascular stiffening, increased autoimmune diseases, and muscle decay. In the context of pediatric syndromes, oxidative stress could play a role in the first order. In fact, our review of the literature showed that in some pathologies, such as fetal alcohol spectrum disorders, oxidative stress related to the intake of ethanol during pregnancy is a main etiological factor determining the associated clinical syndrome. On the contrary, in Williams syndrome, Down syndrome, Marfan syndrome, Gaucher syndrome, ataxia-telangiectasia, autistic spectrum disorder, Fanconi’s anemia, and primitive immunodeficiencies, the increase in oxidative stress is directly associated with the genetic alterations that cause the same pathologies. Although further studies are needed to better understand the relationship between oxidative stress and pediatric diseases, a better knowledge of this crucial issue encourages future therapeutic strategies.

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Section: Pediatrics Syndromes Associated With Oxidative Stressmentioning

confidence: 99%

The Impact of Oxidative Stress on Pediatrics Syndromes

et al. 2022

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“…In the absence of linkage studies, several candidate gene studies were applied to relatively small samples of FMD patients. The search for mutations in candidate genes was motivated by the occurrence of vascular abnormalities mimicking FMD stenosis, aneurysm, or vascular tortuosity in Mendelian connective tissue disorders such as Marfan, Loeys-Dietz, vascular Ehlers-Danlos, or type I neurofibromatosis syndromes [ 26–28 ]. It is, however, unclear whether these lesions arise from the same pathophysiological mechanisms [ 28 , 29 ].…”

Section: Defining the Genetic Model For Fmd And Candidate Gene Studiesmentioning

confidence: 99%

“…The strongest genetic signal in SCAD GWAS was located on chromosome 1, near a disintegrin and metalloproteinase with thrombospondin-like protein 4 ( ADAMTSL4 ) gene, which encodes a protein potentially involved in fibrillin deposition [ 67 , 92 , 93 ]. Another SCAD genetic locus overlaps fibrillin-1 gene ( FBN1 ), the causal gene for Marfan syndrome, also associated with thoracic artery aneurysm and dissection [ 26 ]. Mutations in fibrillar collagen were strongly enriched in SCAD but remain rare in FMD cohorts.…”

Section: Genetic Data Supports Etiological Links Between Fmd and Comm...mentioning

confidence: 99%

The complex genetic basis of fibromuscular dysplasia, a systemic arteriopathy associated with multiple forms of cardiovascular disease

Georges

Bouatia-Naji

2022

Clinical Science

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Artery stenosis is a common cause of hypertension and stroke and can be due to atherosclerosis accumulation in the majority of cases and in a small fraction of patients to arterial fibromuscular dysplasia (FMD). Artery stenosis due to atherosclerosis is widely studied with known risk factors (e.g. increasing age, male gender, and dyslipidemia) to influence its etiology, including genetic factors. However, the causes of noninflammatory and nonatherosclerotic stenosis in FMD are less understood. FMD occurs predominantly in early middle-age women, a fraction of the population where cardiovascular risk is different and understudied. FMD arteriopathies are often diagnosed in the context of hypertension and stroke and co-occur mainly with spontaneous coronary artery dissection, an atypical cause of acute myocardial infarction. In this review, we provide a comprehensive overview of the recent advances in the understanding of molecular origins of FMD. Data were obtained from genetic studies using complementary methodological approaches applied to familial, syndromic, and sporadic forms of this intriguing arteriopathy. Rare variation analyses point toward mechanisms related to impaired prostacyclin signaling and defaults in fibrillar collagens. The study of common variation, mainly through a recent genome-wide association study, describes a shared genetic link with blood pressure, in addition to point at potential risk genes involved in actin cytoskeleton and intracellular calcium homeostasis supporting impaired vascular contraction as a key mechanism. We conclude this review with future strategies and approaches needed to fully understand the genetic and molecular mechanisms related to FMD.

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“…These microfibrils serve as a foundation where elastin is deposited and are important for building a proper elastic framework for providing elasticity to dynamic connective tissues [13]. The structure of these fibrils is stabilised by the epidermal growth factor (EGF), which is arranged in tandem orientation [14]. These EGF prevent the fibrinolysis of the fibrils with the help of calcium-binding EGF (cbEGF).…”

Section: Genetic Basismentioning

confidence: 99%

Cardiac Complications in Marfan Syndrome: A Review

Singh¹,

Wanjari²

2022

Cureus

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Marfan syndrome (MFS) is a rare inherited disorder of the connective tissue with an autosomal dominant mode of inheritance which happens as a result of a mutation in the fibrillin-1 (FBN1) gene located on chromosome 15q21.1. This mutation results in the defective formation of microfibrils and increased levels of active transforming growth factor beta (TGF beta), leading to defective connective tissue synthesis. These changes affect various parts of the body but most notably affected are the heart, eyes, and the musculoskeletal system. The standard presenting features of a person suffering from MFS are tall stature with a large arm span, kyphosis, congenital dislocation of the lens (ectopia lentis) and cardiovascular manifestations. The 2010 modified Ghent criteria are used to diagnose MFS on the basis of parameters such as cardiovascular, eye, and musculoskeletal disorders. The cardiovascular manifestations in a patient with MFS are the leading causes of mortality. The most common and dreaded complication is an aortic aneurysm and subsequent dissection. Cardiomyopathy and arrhythmia are also potential killers in such patients. This article aims to look at the various cardiac complications mentioned above and gain an understanding of their pathogenesis, incidence, and outcome. It also includes a brief overview of the rare complication post-Bentall graft infection, and its cause, diagnosis, and management. Various articles by several different authors from around the world were searched for information regarding the pathogenesis, incidence, and outcomes of these patients and are referenced below.

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Pathophysiology and Pathogenesis of Marfan Syndrome

Cited by 53 publications

References 107 publications

The Impact of Oxidative Stress on Pediatrics Syndromes

The Impact of Oxidative Stress on Pediatrics Syndromes

The complex genetic basis of fibromuscular dysplasia, a systemic arteriopathy associated with multiple forms of cardiovascular disease

Cardiac Complications in Marfan Syndrome: A Review

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