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Marfan Syndrome (marfan + syndrome)

Distribution by Scientific Domains

Life Sciences	50%
Medical Sciences	43%

Selected Abstracts

Mitral Valve Prolapse in Marfan Syndrome: An Old Topic Revisited

ECHOCARDIOGRAPHY, Issue 4 2009
Cynthia C. Taub M.D.
Background: The echocardiographic features of mitral valve prolapse (MVP) in Marfan syndrome have been well described, and the incidence of MVP in Marfan syndrome is reported to be 40,80%. However, most of the original research was performed in the late 1980s and early 1990s, when the diagnostic criteria for MVP were less specific. Our goal was to investigate the characteristics of MVP associated with Marfan syndrome using currently accepted diagnostic criteria for MVP. Methods: Between January 1990 and March 2004, 90 patients with definitive diagnosis of Marfan syndrome (based on standardized criteria with or without genetic testing) were referred to Massachusetts General Hospital for transthoracic echocardiography. Patients' gender, age, weight, height, and body surface area at initial examination were recorded. Mitral valve thickness and motion, the degree of mitral regurgitation and aortic regurgitation, and aortic dimensions were quantified blinded to patients' clinical information. Results: There were 25 patients (28%) with MVP, among whom 80% had symmetrical bileaflet MVP. Patients with MVP had thicker mitral leaflets (5.0 ± 1.0 mm vs. 1.8 ± 0.5 mm, P < 0.001), more mitral regurgitation (using a scale of 1,4, 2.2 ± 1.0 vs. 0.90 ± 0.60, P < 0.0001), larger LVEDD, and larger dimensions of sinus of Valsalva, sinotubular junction, aortic arch, and descending aorta indexed to square root body surface area, when compared with those without MVP. When echocardiographic features of patients younger than 18 years of age and those of patients older than 18 were compared, adult Marfan patients had larger LA dimension (indexed to square root body surface area), larger sinotubular junction (indexed to square root body surface area), and more mitral regurgitation and aortic regurgitation. Conclusions: The prevalence of MVP in Marfan syndrome is lower than previously reported. The large majority of patients with MVP have bileaflet involvement, and those with MVP have significantly larger aortic root diameters, suggesting a diffuse disease process. [source]

Assessment of Carotid Compliance Using Real Time Vascular Ultrasound Image Analysis in Marfan Syndrome

ECHOCARDIOGRAPHY, Issue 4 2009
Anatoli Kiotsekoglou M.D.
Background: Fibrillin-1 deficiency, dysregulated cytokine transforming growth factor-,, and increased collagen deposition related to fibrillin-1 gene mutations could predispose to impaired carotid compliance (CC) in Marfan syndrome (MFS). We sought to detect any alterations in CC using the vascular image analysis system (VIA). Methods and Results: Thirty-two MFS patients, 20 men and 12 women (mean age 34.2 ± 12.05 years), and 29 controls matched for age, sex, and body surface area (BSA) were recruited. The entire length of each carotid system was initially scanned longitudinally using a 14 MHz linear transducer. Then, a stereotactic clamp held the transducer in contact with the carotid artery. Arterial diameter changes during the cardiac cycle were recorded for 1 minute from both right (RCCA) and left common carotid arteries (LCCA) separately using the VIA system. RCCA and LCCA compliance and distensibility measurements were significantly reduced in MFS patients when compared to controls, P < 0.05. RCCA and LCCA intima-media thickness did not differ between patients and controls, P > 0.05. MFS diagnosis and age were associated with reduced CC in both carotid arteries after adjusting for variables such as, sex, BSA, heart rate, beta-blockade, intima-media thickness, and aortic root size. Conclusions: Our findings showed a reduction in CC in adult patients with MFS. This could be attributed to fibrillin-1 deficiency resulting in structural abnormalities in the carotid arterial wall. [source]

Mitral Valve Prolapse in Marfan Syndrome: An Old Topic Revisited

Assessment of Carotid Compliance Using Real Time Vascular Ultrasound Image Analysis in Marfan Syndrome

Generation of mice with a conditional allele for transforming growth factor beta 1 gene

GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 6 2009
Mohamad Azhar
Abstract Transforming growth factor ,1 (TGF,1) is a multifunctional growth factor involved in wound healing, tissue fibrosis, and in the pathogenesis of many syndromic diseases (e.g., Marfan syndrome, Camurati-Engelmann disease) and muscular, neurological, ophthalmic, cardiovascular and immunological disorders, and cancer. Since the generation of Tgfb1 knockout mice, there has been extraordinary progress in understanding its physiological and pathophysiological function. Here, we report the generation of a conditional knockout allele for Tgfb1 in which its exon 6 is flanked with LoxP sites. As proof of principle, we crossed these mice to LckCre transgenic mice and specifically disrupted Tgfb1 in T cells. The results indicate that T-cell-produced TGF,1 is required for normal in vivo regulation of peripheral T-cell activation, maintenance of T-cell homeostasis, and suppression of autoimmunity. genesis 47:423,431, 2009. © 2009 Wiley-Liss, Inc. [source]

Mutation screening of the fibrillin-1 (FBN1) gene in 76 unrelated patients with Marfan syndrome or Marfanoid features leads to the identification of 11 novel and three previously reported mutations,,

HUMAN MUTATION, Issue 5 2002
Kathrin Rommel
Abstract Mutations in the gene encoding fibrillin-1 (FBN1) cause Marfan syndrome (MFS) and other related connective tissue disorders. In this study we performed SSCP to analyze all 65 exons of the FBN1 gene in 76 patients presenting with classical MFS or related phenotypes. We report 7 missense mutations, 3 splice site alterations, one indel mutation, one nonsense mutation and two mutations causing frameshifts: a 16bp deletion and a single nucleotide insertion. 5 of the missense mutations (Y1101C, C1806Y, T1908I, G1919D, C2251R) occur in calcium-binding Epidermal Growth Factor-like (EGFcb) domains of exons 26, 43, 46 and 55, respectively. One missense mutation (V449I) substitutes a valine residue in the non-calcium-binding epidermal growth factor like domain (EGFncb) of exon 11. One missense mutation (G880S) affects the "hybrid" motif in exon 21 by replacing glycine to serine. The 3 splice site mutations detected are: IVS1,1G>A in intron 1, IVS38-1G>A in intron 38 and IVS46+5G>A in intron 46. C628delinsK was identified in exon 15 leading to the substitution of a conserved cysteine residue. Furthermore two frameshift mutations were found in exon 15 (1904-1919del ) and exon 63 (8025insC) leading to premature termination codons (PTCs) in exon 17 and 64 respectively. Finally we identified a nonsense mutation (R429X) located in the proline rich domain in exon 10 of the FBN1 gene. Y1101C, IVS46+5G>A and R429X have been reported before. © 2002 Wiley-Liss, Inc. [source]

A probable case of gigantism in a fifth Dynasty skeleton from the Western Cemetery at Giza, Egypt

INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 4 2005
D. M. MulhernArticle first published online: 31 DEC 200
Abstract Pituitary gigantism is a rare endocrine disorder caused by excess secretion of growth hormone during childhood. Individuals with this condition exhibit unusually tall stature due to prolonged growth as well as associated degenerative changes. Continued secretion of excess growth hormone during adulthood results in acromegaly, a related condition that results in bony overgrowth of the skull, hands and feet. The remains of a large adult male, probably in his late 20s or early 30s, from a Fifth Dynasty tomb (2494,2345 BC) were excavated in 2001 from Cemetery 2500 in the Western Cemetery at Giza, Egypt, as part of the Howard University Giza Cemetery Project. This individual exhibits characteristics of pituitary gigantism, including tall but normally-proportioned stature, delayed epiphyseal union, a large sella turcica, advanced arthritis and a transepiphyseal fracture of the left femoral head. Additional pathological features, including osteopenia and thinness of the parietal bones, suggest that this individual may also have been hypogonadal. Craniometric comparisons with other ancient Egyptian groups as well as modern normal and acromegalic patients show some tendency toward acromegalic skull morphology. Differential diagnosis includes eunuchoid gigantism, Sotos syndrome, Beckwith-Wiedemann syndrome, Marfan syndrome, homocystinuria, Weaver syndrome and Klinefelter syndrome. In conclusion, the pathological features associated with this skeleton are more consistent with pituitary gigantism than any of the other syndromes that result in skeletal overgrowth. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Prenatal Marfan syndrome: report of one case and review of the literature

PRENATAL DIAGNOSIS, Issue 8 2006
K. R. M. Lopes
Abstract Objectives Our objective was to describe the features of prenatal Marfan syndrome. Methods Doppler fetal echocardiograms were performed. The morphology and rhythm of the fetal heart were examined sequentially. Results The case was referred because of cardiomegaly and dilated great vessels. Sequential Doppler echocardiographic evaluation led to the diagnosis of prenatal Marfan syndrome. The main features are cardiomegaly, dysplastic atrioventricular valves with tricuspid regurgitation and dilated great vessels, which can be aneurysmal at their origin. The fetus died in utero at 39 weeks of gestation because of cardiac failure. Pathological study confirmed the Marfan habitus and complications. Molecular genetic study showed a de novo point mutation in exon 26 of the FBN1 gene. Conclusion We report a case of prenatal Marfan syndrome diagnosed by sequential evaluation of the cardiac signs, which are essential for prenatal diagnosis. The prognosis seems as poor as the neonatal one. The prenatal diagnosis is essential for adequate counselling. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Mutation spectrum of the fibrillin-1 (FBN1) gene in Taiwanese patients with Marfan syndrome

ANNALS OF HUMAN GENETICS, Issue 6 2009
Chia-Cheng Hung
SUMMARY The aim of this study was to establish a national database of mutations in the fibrillin-1 (FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population. In this study, we screened 294 patients from 157 families for the presence of FBN1 mutations using polymerase chain reaction/ denaturing high performance liquid chromatography (PCR/DHPLC). We identified 56 mutations in 62 of the 157 (40%) families including 49 single-base substitutions (36 missense mutations, seven nonsense mutations, and six splicing sites), one small insertion, four small deletions, one small indel (insertion and deletion), and one exonic deletion (Exon 36). When family history was taken into consideration, the mutation detection rate rose to 91% (29 of 32). We further investigated the phenotypic data and found that one third (47 of 157) of the families fit the Ghent criteria for MFS. Based on that data, the mutation rate was 98% (46/47). That finding implies that family history and the Ghent criteria play a more important role than clinical manifestations in establishing a clinical diagnosis of Marfan syndrome. Among the 56 mutations found in this study, 40 (71%) have not been registered in the Human Gene Mutation Database (HGMD) or in the Universal Mutation Database (UMD). This is the first study of the mutation spectrum of MFS in a cohort of patients in Taiwan. The database is expected to considerably improve genetic counseling for and medical care of MFS families. [source]

Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2009
HH Clarice Yang
Background and purpose:, During development of thoracic aortic aneurysms in a mouse model of Marfan syndrome, upregulation of matrix metalloproteinase (MMP)-2 and -9 was accompanied by compromised aortic constriction and endothelium-dependent relaxation. Losartan has been proposed for the prevention of thoracic aortic aneurysm. We hypothesized that losartan would suppress MMP-2/-9 activation and improve aortic vasomotor function in this model. Experimental approach:, A well-characterized mouse model of Marfan syndrome (Fbn1C1039G/+) was used. Starting at 6 weeks old, Marfan mice were untreated or given losartan (0.6 g·L,1 in drinking water, n= 30). The littermate Fbn1+/+ mice served as control. Thoracic aortas were studied at 3, 6 and 9 months by histology and by contractility assays in isolated segments in vitro. Key results:, Losartan improved elastic fibre organization and increased aortic breaking stress. Losartan reduced the activity and protein expression of MMP-2 and MMP-9 at all ages. Aortic constriction in response to membrane depolarization or phenylephrine was increased by losartan at 3 and 9 months by 100,200%. Active force of aortic smooth muscle was also increased at 6 and 9 months. Acetylcholine-induced endothelium-dependent relaxation was improved by 30% after 3 months of losartan treatment, but such improvement disappeared with longer duration of treatment, accompanied by reduced phosphorylation of endothelial nitric oxide (NO) synthaseSer1177, AktThr308 and AktSer473, compared with the control. Conclusions and implications:, Losartan improved the contractile function of aorta and reduced MMP activation. However, the endothelial NO pathway remained suppressed in the thoracic aorta during losartan treatment, which might limit its long-term benefits in Marfan syndrome. [source]

Safety, tolerability, and efficacy of endoscopic low-pressure liquid nitrogen spray cryotherapy in the esophagus

DISEASES OF THE ESOPHAGUS, Issue 1 2010
Bruce D. Greenwald
SUMMARY Endoscopic cryotherapy is a new technique for ablation of esophageal dysplasia and neoplasia. Preliminary studies have shown it to be safe and effective for this indication. The objective of this study is to characterize safety, tolerability, and efficacy of low-pressure liquid nitrogen endoscopic spray cryotherapy ablation in a large cohort across multiple study sites. Parallel prospective treatment studies at four tertiary care academic medical centers in the U.S. assessed spray cryotherapy in patients with Barrett's esophagus with or without dysplasia, early stage esophageal cancer, and severe squamous dysplasia who underwent cryotherapy ablation of the esophagus. All patients were contacted between 1 and 10 days after treatment to assess for side effects and complications of treatment. The main outcome measurement was the incidence of serious adverse events and side effects from treatment. Complete response for high-grade dysplasia (HGD) (CR-HGD), all dysplasia (CR-D), intestinal metaplasia (CR-IM) and cancer (CR-C) were assessed in patients completing therapy during the study period. A total of 77 patients were treated for Barrett's high-grade dysplasia (58.4%), intramucosal carcinoma (16.9%), invasive carcinoma (13%), Barrett's esophagus without dysplasia (9.1%), and severe squamous dysplasia (2.6%). Twenty-two patients (28.6%) reported no side effects throughout treatment. In 323 procedures, the most common complaint was chest pain (17.6%) followed by dysphagia (13.3%), odynophagia (12.1%), and sore throat (9.6%). The mean duration of any symptoms was 3.6 days. No side effects were reported in 48% of the procedures (155/323). Symptoms did not correlate with age, gender, diagnosis, or to treatment early versus late in the patient's or site's experience. Logit analysis showed that symptoms were greater in those with a Barrett's segment of 6 cm or longer. Gastric perforation occurred in one patient with Marfan's syndrome. Esophageal stricture developed in three, all successfully treated with dilation. In 17 HGD patients, cryotherapy produced CR-HGD, CR-D, and CR-IM of 94%, 88%, and 53%, respectively. Complete regression of cancer and HGD was seen in all seven patients with intramucosal carcinoma or stage I esophageal cancer. Endoscopic spray cryotherapy ablation using low-pressure liquid nitrogen in the esophagus is safe, well-tolerated, and efficacious. [source]

Symposium on the musculoskeletal aspects of marfan syndrome: Meeting report and state of the science

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2007
Kevin B. Jones
Abstract The National Marfan Foundation sponsored a symposium in August 2005 to review recent progress in the area of Marfan-related musculoskeletal research. Orthopaedic surgeons, molecular geneticists, medical geneticists, and pain specialists met to review a variety of topics. This report reviews and summarizes the proceedings of the symposium, with emphasis on future directions for study that were identified in the course of the meeting. Areas covered include clinical detection, diagnosis, growth, spine deformity, molecular mechanisms, dural ectasia, protrusio acetabuli, and pain in Marfan syndrome. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 2007 [source]