1/13. Novel exon skipping mutation in the fibrillin-1 gene: two 'hot spots' for the neonatal marfan syndrome.The marfan syndrome is an autosomal dominant heritable disorder of connective tissue that involves principally the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum, the neonatal marfan syndrome (nMFS), is characterized by pronounced atrioventricular valve dysfunction, and death often occurs within the first year of life due to congestive heart failure. Mutations in the gene coding for fibrillin-1, FBN1, are known to cause marfan syndrome, and have been identified in almost all exons of FBN1. Here, we describe a novel mutation affecting the invariant 1 position of the splice donor site in intron 31, associated with skipping of exon 31, in a patient with nMFS. Published reports of nMFS are reviewed and a strict definition for nMFS is suggested. If this definition is used, all nMFS mutations reported to date lie in one of two hot spots, comprising mainly missense mutations in FBN1 exons 24-27 and mutations causing skipping of exon 31 or 32.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
2/13. Novel approach to the molecular diagnosis of marfan syndrome: application to sporadic cases and in prenatal diagnosis.marfan syndrome is an autosomal dominant disorder affecting the skeletal, ocular, and cardiovascular systems. Defects in the gene that encodes fibrillin-1 (FBN1), the main structural component of the elastin-associated microfibrils, are responsible for the disorder. Molecular diagnosis in families with marfan syndrome can be undertaken by using intragenic FBN1 gene markers to identify and track the disease allele. However, in sporadic cases, which constitute up to 30% of the total, dna-based diagnosis cannot be performed using linked markers but rather requires the identification of the specific FBN1 gene mutation. Due to the size and complexity of the FBN1 gene, identification of a causative marfan syndrome mutation is not a trivial undertaking. Herein, we describe a comprehensive approach to the molecular diagnosis of marfan syndrome that relies on the direct analysis of the FBN1 gene at the cDNA level and detects both coding sequence mutations and those leading to exon-skipping, which are often missed by analysis at the genomic dna level. The ability to consistently determine the specific FBN1 gene mutation responsible for a particular case of marfan syndrome allows both prenatal and pre-implantation diagnosis, even in sporadic instances of the disease.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
3/13. Coexistent Marfan's syndrome and ankylosing spondylitis: a case report.We report on a 46-year-old man with a 4-year history of predominantly nocturnal pain at the thoracic and lumbar spine as well as accompanying morning stiffness and episodes of alternating buttock pain. At physical examination the patient presented with the typical traits for Marfan's syndrome (MFS), along with limitation of both chest expansion and movement in all planes of the lumbar spine. Pelvic and lumbar spine radiographs showed findings consistent with ankylosing spondylitis (AS). Laboratory tests were consistent with an inflammatory state and HLA typing was positive for the B27 antigen. Transthoracic echocardiography showed prolapse of the posterior mitral leaflet and mild aortic insufficiency. We diagnosed co-existent MFS and AS. The association of these two pathologies is particularly interesting, owing to the co-existence of hypermobility of peripheral joints due to MFS ligamentous hyperlaxity, and the reduction of both axial skeleton motility and chest expansion related to AS. As both of these diseases may damage the cardiovascular system over time, follow-up with echocardiography monitoring is indispensable.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
4/13. Marfan's syndrome, dextrocardia and situs inversus associated with discrete subaortic stenosis and aortic insufficiency in an adult female: case report.Marfan's syndrome is an inherited connective tissue defect that affects many organs, especially of the musculoskeletal, ophthalmic and cardiovascular systems, and may be associated with some rare conditions. Here, we report the first known case of Marfan's syndrome, combined with situs inversus totalis with dextrocardia and discrete subaortic stenosis and aortic insufficiency in a 22-year-old woman.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
5/13. Fibrillin-1 (FBN1) gene frameshift mutations in Marfan patients: genotype-phenotype correlation.marfan syndrome (MFS) is a multisystemic disease associated with mutations in the fibrillin-1 gene. Most of the reported mutations are missense substitutions mainly affecting the epidermal growth factor (EGF)-like protein domain structure and the calcium-binding (cb) site. The aim of our study was to investigate the correlation between fibrillin-1 frameshift mutations and the clinical phenotype in patients affected by MFS. In 48 out of 66 Marfan patients a pathogenetic mutation was found. We detected novel mutations causing premature termination codon in exons 19, 37, 40 and 41 of four Italian patients. The first mutation in exon 19 (cbEGF #8 domain) results in a clinical phenotype involving mainly the skeletal and cardiovascular systems. Interestingly, we noticed that, while mutations in exons 37 and 41 (eight cysteine domains #4 and #5) are milder, the mutation in exon 40 (cbEGF #24 domain) is more severe and causes major cardiovascular involvement with thoracic and abdominal aortic aneurysms. It is noteworthy that the degree of the severity in the phenotype of one of our patients and another from the literature carrying a mutation in exon 41 could be explained with alterations in mRNA expression.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
6/13. Caring for a Marfan patient with cardiovascular complications.The marfan syndrome is a heritable disorder of connective tissue associated with characteristic abnormalities of the skeletal, ocular and cardiovascular systems. Common cardiovascular manifestations of this syndrome are mitral valve prolapse with mitral regurgitation and dilatation of the ascending aorta resulting in aortic insufficiency, dissection, aneurysm and/or rupture. Although the prognosis for a patient with the marfan syndrome is significantly more favorable than it was ten years ago, the cardiovascular complications continue to greatly reduce life expectancy. This article presents an overview of the marfan syndrome including: history and epidemiology, clinical manifestations, diagnostic criteria, surgical intervention and follow-up. A case study is outlined which focuses on priority nursing diagnoses and a plan of care.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
7/13. Abdominal aortic dissection with acute mesenteric ischemia in a patient with marfan syndrome.marfan syndrome is an autosomal dominant inherited disorder of connective tissue, with various complications manifested primarily in the cardiovascular system. It potentially leads to aortic dissection and rupture, these being the major causes of death. We report a patient who complained of acute abdominal pain, which presented as acute mesenteric ischemia combined with abdominal aortic dissection. echocardiography showed enlargement of the aortic root and mitral valve prolapse. Abdominal computed tomography scan revealed acute mesenteric ischemia due to abdominal aortic dissection. Finally, the patient underwent surgery of aortic root replacement and had a successful outcome. Therefore, we suggest that for optimal risk assessment and monitoring of patients with marfan syndrome, both aortic stiffness and the diameter of the superior mesenteric vein compared with that of the superior mesenteric artery are useful screening methods to detect acute mesenteric ischemia secondary to abdominal aortic dissection. early diagnosis and early treatment can decrease the high mortality rate of patients with marfan syndrome.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
8/13. marfan syndrome. What you need to know.marfan syndrome is a heritable disorder of the connective tissue. The major abnormalities occur in the ocular, skeletal, and cardiovascular systems, with variable expression in different patients. Most common are dislocated lens, which may or may not affect visual acuity, arachnodactyly, and mitral valve prolapse and aortic root dilatation. Cardiovascular complications cause about 90% of the excess early mortality seen with the syndrome. With proper management, including annual examination, some of the problems associated with these abnormalities may be avoided. The biochemical explanation for the disorder is not clear. Some investigators maintain that a defect in collagen is responsible, while others point to elastin as the culprit. Further studies are needed to disclose the exact defect; both proteins may be found to play a role in this highly variable disorder.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
9/13. Mitral valve disease in Marfan's syndrome.Cardiovascular disease in Marfan's syndrome presenting in childhood affects the mitral valve more often than the aortic valve or the aorta, as in adults. Early evaluation of the cardiovascular system is necessary for any child in whom Marfan's syndrome is suspected.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
10/13. Case report and study of collagen metabolism in Marfan's syndrome.The case report on a 33 year old woman with prominent features of Marfan's syndrome is presented. Characteristic signs were seen in the bones, the eyes, the cardiovascular system, and the lungs. Due to regurgitation of both the aortic and mitral valves and an aneurysm of the ascending aorta a double valve replacement was made, including a prosthesis of the aorta. The problems of early diagnosis and therapy of the life-threatening cardiovascular complications are discussed. Tissue specimens from the aorta were analysed histochemically and biochemically. histology showed a typical necrosis of the media with cyst formation. Biochemical analysis by in vitro labeling of collagen in tissue explants and by electron microscopical evaluation showed proportions of type I and type III collagen which were significantly different from controls. In both the media and the adventitia the amount of type I collagen was drastically reduced as shown by quantitation of collagen and procollagen. fibroblasts derived from the skin of the patient showed a normal content of type I and type III collagen. It is conceivable that the reduced content of type I collagen in the aortic wall is responsible for the weakness of the vessel wall causing formation of aneurysm and its sequelae.- - - - - - - - - - ranking = 1keywords = cardiovascular system (Clic here for more details about this article) |
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