scholarly journals Marfan's syndrome: an overview

2010 ◽  
Vol 128 (6) ◽  
pp. 360-366 ◽  
Author(s):  
Shi-Min Yuan ◽  
Hua Jing
Keyword(s):  
Connective Tissue ◽  
Aortic Surgery ◽  
Clinical Manifestations ◽  
The Body ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Contributory Factor ◽  
Marfan’S Syndrome ◽  
Marfan's Syndrome ◽  
Organ Systems

Marfan's syndrome is an autosomal dominant condition with an estimated prevalence of one in 10,000 to 20,000 individuals. This rare hereditary connective tissue disorder affects many parts of the body. The diagnosis of Marfan's syndrome is established in accordance with a review of the diagnostic criteria, known as the Ghent nosology, through a comprehensive assessment largely based on a combination of major and minor clinical manifestations in various organ systems and the family history. Aortic root dilation and mitral valve prolapse are the main presentations among the cardiovascular malformations of Marfan's syndrome. The pathogenesis of Marfan's syndrome has not been fully elucidated. However, fibrillin-1 gene mutations are believed to exert a dominant negative effect. Therefore, Marfan's syndrome is termed a fibrillinopathy, along with other connective tissue disorders with subtle differences in clinical manifestations. The treatment may include prophylactic β-blockers and angiotensin II-receptor blockers in order to slow down the dilation of the ascending aorta, and prophylactic aortic surgery. Importantly, β-blocker therapy may reduce TGF-β activation, which has been recognized as a contributory factor in Marfan's syndrome. The present article aims to provide an overview of this rare hereditary disorder.

Current insights in diagnosis and management of the cardiovascular complications of Marfan's syndrome

2002 ◽  
Vol 12 (4) ◽  
pp. 320-327 ◽  
Author(s):  
Gijs J. Nollen ◽  
Maarten Groenink ◽  
Ernst E. van der Wall ◽  
Barbara J. M. Mulder
Keyword(s):  
Connective Tissue ◽  
Medical Treatment ◽  
Clinical Features ◽  
Cardiovascular Complications ◽  
Chromosome 15 ◽  
Marfan’S Syndrome ◽  
Marfan's Syndrome ◽  
Diagnosis And Management ◽  
Fibrillin 1

AbstractMarfan's syndrome is an inherited disorder of connective tissue, caused by mutations in the fibrillin-1 gene located on chromosome 15. Diagnosis is still based on a combination of major and minor clinical features. Prognosis is mainly determined by the cardiovascular complications. Advances in surgical and medical treatment for these complications have dramatically improved the prognosis of the syndrome.

scholarly journals Recurrent respiratory viral diseases and chronic sequelae due to dominant negative IFIH1

2020 ◽  
Author(s):  
Christin L Deal ◽  
Timothy J Thauland ◽  
Rebecca Signer ◽  
Stanley F Nelson ◽  
Hane Lee ◽  
...  
Keyword(s):  
Viral Infections ◽  
Respiratory Infections ◽  
Clinical Manifestations ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Negative Effect ◽  
Respiratory Viral Infections ◽  
Compound Heterozygous Variants

Viral respiratory infections are the most common childhood infection worldwide. However, even common pathogens can have significant consequences in the context of patients with primary immunodeficiency diseases. More than half or viral infections annually are due to rhinovirus/enterovirus strains. Most clinical manifestations of viral infection are mild. However 3% of cases result in hospitalization in patients who have no other known risk factors. These patients may have an inborn error of immunity, a genetic susceptibility to viral infections. Here we present the case of an adult male who suffered respiratory viral infections his whole life and developed chronic, inflammatory damage to sinuses and lungs as a consequence. Genomic sequencing identified compound heterozygous variants in the IFIH1 gene, encoding the protein Melanoma Differentiation Association Protein 5 (MDA5), a RIG-I-like cytoplasmic sensor of RNA intracellular infections. We show a dominant negative effect on these variants on the level of interferon-induced expression of MDA5 protein. This work supports that loss-of-function variants in IFIH1 affect the sensing of viral infections. Underlying genomic variants may dictate the point at which recurrent, respiratory viral infections leave commonplace experience and incur lasting damage.

scholarly journals Pulmonary Hypertension Associated With Scleroderma and Connective Tissue Disease: Potential Molecular and Cellular Targets

2017 ◽  
Vol 16 (2) ◽  
pp. 61-67
Author(s):  
Maria Trojanowska
Keyword(s):  
Pulmonary Hypertension ◽  
Connective Tissue ◽  
Connective Tissue Disease ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Connective Tissue Diseases ◽  
Clinical Manifestations ◽  
Response To Treatment ◽  
Organ Systems

Systemic sclerosis (SSc) is characterized by autoimmunity, small-vessel vasculopathy, and fibrosis causing damage in multiple organ systems. Pulmonary arterial hypertension (PAH) is a serious and often fatal complication of SSc, occurring in patients with the limited (lcSSc) and diffuse (dcSSc) forms of the disease and affecting 8% to 15% of patients.12 While pulmonary hypertension associated with connective tissue disease (CTD-PAH) has similar clinical features as idiopathic PAH, 1-year survival and freedom from hospitalization are lower in CTD-PAH.3 SSc-PAH has the worst 1-year survival rate at 82% compared with other connective tissue diseases, including systemic lupus erythematosus, mixed connective tissue disease, and rheumatoid arthritis.34 Despite the recent progress in the development of disease-targeted therapies, patients with SSc-PAH have a poorer response to treatment and a worse prognosis than other subgroups of PAH.1 Autoimmunity and prolonged vasculopathy preceding the development of clinical manifestations of SSc-PAH may play a critical role in the poorer outcome of SSc-PAH patients.1 This article will provide an overview of the recent findings related to cellular and molecular mechanisms associated with the development of PAH, with an emphasis on SSc-PAH.

Detection of dural ectasia in diagnosis of Marfan’s syndrome

VASA ◽  
2008 ◽  
Vol 37 (4) ◽  
pp. 364-370 ◽  
Author(s):  
Jonszta ◽  
Prochazka ◽  
Czerny ◽  
Vavrova ◽  
Chmelova
Keyword(s):  
Spinal Canal ◽  
Connective Tissue Disorder ◽  
Whole Body ◽  
Marfan’S Syndrome ◽  
Lumbosacral Region ◽  
Marfan's Syndrome ◽  
Dural Ectasia ◽  
Dural Sac ◽  
Whole Body Ct ◽  
Organ Systems

Background: Marfan’s syndrome is an inherited connective tissue disorder that affects many organ systems and has widespread phenotype expression. The diagnosis is therefore made by phenotype assessment. Dural ectasia has been classified as a major diagnostic criterium with a prevalence of over 90% in patients with Marfan’s syndrome. The objective of this study determine the feasibility of performing CT angiographic examination of aorta and large vessels for dural ectasia grading in a single CT exam of patients with Marfan’s syndrome. Patients and methods: 7 examinations in Marfan patients were performed of which 6 were CTA. In all exams the aorta was evaluated and simultaneously the lumbosacral region of the spine was well delineated. We performed calculation of spinal canal (SCI) and dural sac (DSI) indices and also qualitative grading of dural sac involvement. Results: In 4 patients both SCI (> 4,50) and DSI (> 3,75) fulfil the diagnostic criteria of Marfan’s syndrome. In 1 patient complete spondyloptosis was detected. Conclusions: Whole body CT examination is the perfect tool for both aorta and spinal canal evaluation. Despite differences in spinal canal grading methods in all of our patients significant changes of the spinal canal in the lumbosacral region were detected. Dural ectasia is easy to detect and quantify and may therefore be used as a sensitive and specific sign of Marfan’s syndrome.

Clinical Manifestations of Scleroderma

1995 ◽  
Vol 16 (2) ◽  
pp. 49-49
Author(s):  
Patricia L. Haber
Keyword(s):  
Systemic Sclerosis ◽  
Connective Tissue ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Localized Scleroderma ◽  
Unknown Etiology ◽  
Collagen Deposition ◽  
Muscle Fibrosis ◽  
Favorable Prognosis ◽  
Organ Systems

Scleroderma is a connective tissue disease of unknown etiology. Its most characteristic feature is thickening of the skin due to increased collagen deposition. However, the disease may involve multiple other organ systems. Two broad categories of scleroderma have been defined: localized and systemic. Although all forms of scleroderma are rare, localized scleroderma occurs more frequently than systemic sclerosis and has a more favorable prognosis. Several types of localized scleroderma exist. Morphea is characterized by the presence of one or more patches of hard, ivory-colored skin lesions. They begin with erythema and progress to nonpitting edema before becoming sclerotic. The margins of active lesions often have a violaceous hue. Underlying muscle fibrosis and atrophy may occur.

Characterization of micro-RNA Profile in the Blood of Patients with Marfan's Syndrome

2017 ◽  
Vol 66 (01) ◽  
pp. 116-124 ◽  
Author(s):  
Nicole Ludwig ◽  
Tanja Rädle-Hurst ◽  
Andreas Keller ◽  
Lars Motsch ◽  
Ina Marsollek ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Clinical Manifestations ◽  
Micro Rna ◽  
Cellular Interaction ◽  
Marfan’S Syndrome ◽  
Marfan's Syndrome ◽  
Micro Rnas ◽  
Wide Range ◽  
Mirna Abundance

Background Marfan's syndrome (MFS) is an autosomal dominant inheritance disorder with a 1/5,000 live-birth prevalence. It is characterized by a wide range of clinical manifestations with more than 3,000 mutations identified in the FBN1 gene. In this study, we aimed to determine if specific patterns of circulating micro-RNAs (miRNAs) are associated with MFS-associated with cardiovascular diseases. Methods Microarray-based miRNA profiling was performed on blood samples of 12 MFS patients, and 12 healthy volunteers (HVs) controls and the differences in miRNA abundance between the two groups were validated using independent cohorts of 22 MFS and of 22 HV controls by real-time quantitative polymerase chain reaction (RT-qPCR). Enrichment analyses of altered miRNA abundance were predicted using bioinformatics tools. Results Altered miRNA abundance levels were determined between MFS (n = 34) and HVs (n = 34). In a screening phase, we analyzed 12 patients with MFS and 12 HVs by miRNA microarray. We found 198 miRNAs that were significantly altered in MFS patients as compared with HVs, including 16 miRNAs with a more than 1.5-fold change. Out of these 16 miRNAs, 10 showed a decreased abundance and 6 showed an increased abundance. In the validation phase, we analyzed independent cohorts of 22 MFS and of 22 HV controls by RT-qPCR. We confirmed the direction of abundance changes and the significance of different abundances between MFS patients and HVs for four miRNAs, namely, miR-362–5p, miR-339–3p, miR-340–5p, and miR-210–3p. Only the miR-150–5p showed a significant correlation with mitral valve prolapse (p = 0.010). The predicted targets for the validated miRNAs were associated with signal transduction, tissue remodeling, and cellular interaction pathways. Conclusion The altered abundance level of different miRNAs in whole blood of MFS patients lays the ground to the development of novel diagnostic approaches with altered miRNAs levels associated with MFS with manifestations associated with cardiovascular diseases.

scholarly journals Pregnancy after Aortic Root Replacement in Marfan's Syndrome: A Case Series and Review of the Literature

2018 ◽  
Vol 08 (04) ◽  
pp. e234-e240 ◽  
Author(s):  
Dominique Williams ◽  
Kathryn Lindley ◽  
Melissa Russo ◽  
Jennifer Habashi ◽  
Harry Dietz ◽  
...  
Keyword(s):  
Literature Review ◽  
Aortic Dissection ◽  
Aortic Root ◽  
Aortic Surgery ◽  
Tertiary Care ◽  
Case Series ◽  
Aortic Root Replacement ◽  
Marfan’S Syndrome ◽  
Marfan's Syndrome ◽  
Case Series Study

Objectives We sought to characterize pregnancy-related aortic complications in women with Marfan's syndrome who had prior aortic root replacement. Study Design This is a retrospective case series study and literature review of women with Marfan's syndrome with pregnancy after aortic root replacement. We surveyed women with Marfan's syndrome who had successful pregnancy after aortic root replacement using the Marfan Foundation Website and from two large tertiary care Marfan's clinics. Clinical data, counseling information, and details of pregnancy-related aortic complications were compiled. A literature review was performed assessing aortic outcomes in women with Marfan's syndrome with pregnancy after aortic surgery. Results Fourteen women with 20 pregnancies were identified. Two women had three pregnancies following root replacement for aortic dissection. There were no aortic dissections during the 20 pregnancies. In contrast, aortic dissection was frequently reported in the literature. Conclusions Women with Marfan's syndrome who become pregnant following aortic root replacement remain at risk for distal aortic dissection related to pregnancy. The exact risk is difficult to quantify but is not zero and women should be counseled accordingly.

A Novel Mutation in EFNB1, Probably with a Dominant Negative Effect, Underlying Craniofrontonasal Syndrome

2006 ◽  
Vol 43 (2) ◽  
pp. 152-154 ◽  
Author(s):  
Vorasuk Shotelersuk ◽  
Pichit Siriwan ◽  
Surasawadee Ausavarat
Keyword(s):  
Amino Acids ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Dominant Negative ◽  
Soluble Form ◽  
Dominant Negative Effect ◽  
Truncated Protein ◽  
Frontonasal Dysplasia ◽  
Thai Woman ◽  
Negative Effect

Craniofrontonasal syndrome (CFNS) is an X-linked disorder whose main clinical manifestations include coronal craniosynostosis and frontonasal dysplasia. Very recently, CFNS was shown to be caused by mutations in EFNB1 encoding ephrin-B1, and 20 mutations have been described. We report a Thai woman with CFNS, in whom a novel mutation was discovered: c.685_686insG, in exon 5 of EFNB1. It is the first insertion and the most 3′ point mutation in EFNB1 reported to date. The mutation is expected to result in a truncated ephrin-B1 of 230 amino acids, composed of a nearly complete extracellular part of ephrin-B1 with no transmembrane and cytoplasmic domains. This truncated protein might become a soluble form of the ligand, which previously was shown to be able to bind to receptors, but fail to cluster and to activate them—in other words, acting as a dominant negative protein. Nonetheless, further studies to detect the protein are needed to substantiate the hypothesis.

scholarly journals Candida albicans—The Virulence Factors and Clinical Manifestations of Infection

2021 ◽  
Vol 7 (2) ◽  
pp. 79
Author(s):  
Jasminka Talapko ◽  
Martina Juzbašić ◽  
Tatjana Matijević ◽  
Emina Pustijanac ◽  
Sanja Bekić ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Oral Candidiasis ◽  
Clinical Manifestations ◽  
The Body ◽  
Host Immune System ◽  
Normal Flora ◽  
Virulence Traits ◽  
Organ Systems ◽  
Wide Range

Candida albicans is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals’ skin. In 50% of the population, C. albicans is part of the normal flora of the microbiota. The various clinical manifestations of Candida species range from localized, superficial mucocutaneous disorders to invasive diseases that involve multiple organ systems and are life-threatening. From systemic and local to hereditary and environmental, diverse factors lead to disturbances in Candida’s normal homeostasis, resulting in a transition from normal flora to pathogenic and opportunistic infections. The transition in the pathophysiology of the onset and progression of infection is also influenced by Candida’s virulence traits that lead to the development of candidiasis. Oral candidiasis has a wide range of clinical manifestations, divided into primary and secondary candidiasis. The main supply of C. albicans in the body is located in the gastrointestinal tract, and the development of infections occurs due to dysbiosis of the residential microbiota, immune dysfunction, and damage to the muco-intestinal barrier. The presence of C. albicans in the blood is associated with candidemia–invasive Candida infections. The commensal relationship exists as long as there is a balance between the host immune system and the virulence factors of C. albicans. This paper presents the virulence traits of Candida albicans and clinical manifestations of specific candidiasis.

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