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Toshiyuki Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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Marfanoid hypermobility caused by an 862 kb deletion of Xq22.3 in a patient with Sotos syndrome.
American journal of medical genetics. Part A, 2011Co-Authors: Keiko Shimojima, Tohru Okanishi, Toshiyuki YamamotoAbstract:Sotos syndrome is a rare genetic disorder characterized by overgrowth associated with macrocephaly and delayed psychomotor development. Patients with Sotos syndrome show 5q35 deletions involving NSD1 or its point mutations. We identified the common 5q35 deletion in a patient with atypical Sotos syndrome manifesting extremely severe developmental delay, joint hypermobility, and skin hyperextensibility, which are recognized as Marfanoid hypermobility syndrome. Further analyses were performed to identify the genetic cause of these additional findings. aCGH analysis revealed an additional 862 kb deletion of Xq22.3 in this patient, which was inherited from his healthy mother. The deleted region included five genes, including the nik-related kinase gene (NRK), which would be a candidate gene for the patient's Marfanoid hypermobility, because it is a member of the glucokinase subfamily that are involved in activating the JNK pathway, and is expressed in developing skeletal musculature. Severe developmental delay seen in the patient may be derived from position effect of the deletion for neighboring interleukin 1 receptor accessory protein-like 2 gene (IL1RAPL2), which is a candidate gene for X-linked mental retardation.
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Marfanoid hypermobility caused by an 862 kb deletion of Xq22.3 in a patient with Sotos syndrome.
American Journal of Medical Genetics Part A, 2011Co-Authors: Keiko Shimojima, Tohru Okanishi, Toshiyuki YamamotoAbstract:Sotos syndrome is a rare genetic disorder characterized by overgrowth associated with macrocephaly and delayed psychomotor development. Patients with Sotos syndrome show 5q35 deletions involving NSD1 or its point mutations. We identified the common 5q35 deletion in a patient with atypical Sotos syndrome manifesting extremely severe developmental delay, joint hypermobility, and skin hyperextensibility, which are recognized as Marfanoid hypermobility syndrome. Further analyses were performed to identify the genetic cause of these additional findings. aCGH analysis revealed an additional 862 kb deletion of Xq22.3 in this patient, which was inherited from his healthy mother. The deleted region included five genes, including the nik-related kinase gene (NRK), which would be a candidate gene for the patient's Marfanoid hypermobility, because it is a member of the glucokinase subfamily that are involved in activating the JNK pathway, and is expressed in developing skeletal musculature. Severe developmental delay seen in the patient may be derived from position effect of the deletion for neighboring interleukin 1 receptor accessory protein-like 2 gene (IL1RAPL2), which is a candidate gene for X-linked mental retardation. © 2011 Wiley-Liss, Inc.
Ekaterina Luneva - One of the best experts on this subject based on the ideXlab platform.
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P1448 Thoracic aorta and circulating transforming growth factor-b in marfan syndrome and Marfanoid habitus
European Heart Journal - Cardiovascular Imaging, 2020Co-Authors: Eduard Malev, Svetlana V. Reeva, Eugeniy Timofeev, Ekaterina LunevaAbstract:Abstract Purpose Current understanding of the pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MS) focuses upon abnormal activity of the transforming growth factor beta (TGF-β) signalling pathway. Circulating TGF-β predicts cardiovascular events in patients with MS and is elevated in the entire spectrum of aortic syndromes. Marfanoid habitus (MH) patients not meeting the MS criteria (TAA, ectopia lentis, family history), but share the same skeletal features and are the part of the Marfan continuum. Our aim was to evaluate the possible role of elevated TGF-β level in the aortic dilatation at mid-term follow-up in Marfanoid habitus patients. Methods 33 consecutive patients with a presumptive clinical diagnosis of Marfan syndrome were referred to Almazov centre and enrolled in our observational, prospective, single-center study. Nine of them (mean age 27.9 ± 9.3) fulfilled diagnosis of MS according to revised Ghent criteria. 24 subjects (mean age 21.8 ± 3.4) with skeletal features of Marfanoid habitus have had no major findings of MS. Proximal aortic segments were visualized in the parasternal long-axis and suprasternal views. Concentration of TGF-β1 and TGF-β2 in serum was determined using a test system Human Platinum ELISA. End points analyzed during 5 years of follow-up were mortality, aortic-related events, and aortic dimension changes. Results During 122 person-years of the follow-up (median 5.1 years) no deaths or aortic-related events occurred in Marfanoid habitus patients. TGF-β1 and TGF-β2 serum levels were elevated in patients with Marfanoid habitus (14.2 ± 27.6 and 2.1 ± 1.7 ng/ml, respectively) but were lower than in MS group (44.6 ± 47.3 ng/ml, p = 0.03 and 2.7 ± 1.7 ng/ml, p = 0.39, respectively). A high TGF-β1 serum level (cutoff >14.75 ng/ml, provided by the manufacturer of our TGF-β assay) was detected in 44% and TGF-β2 (>2.0 ng/ml) in majority patients (67%) of the MS group. In Marfanoid habitus group we found a high TGF-β1 serum level only in 4 (17%) patients and TGF-β2 in 9 (38%) patients. Aortic diameter at the sinuses of Valsalva and Z-score were significantly lower in Marfanoid habitus group (29.2 ± 2.8 mm and 1.56 ± 0.93) than in MS patients (43.1 ± 15.1 mm, p = 0.0007 and 6.86 ± 5.83, p = 0.004) at the beginning of study and significantly increased during the follow-up (31.3 ± 2.9 mm and 1,69 ± 0,15, p < 0.001 for both). There was no correlation between TGF-β level and aortic dimensions in patients with MS and Marfanoid habitus. Conclusion In young adults with Marfanoid habitus and the current absence of ascending aortic aneurysm we found the increased TGF-β level and aortic root enlargement during the follow-up. High TGF-β serum level may contribute to the excessive progression of aortic dilatation later over mid-to-late aging and requires further investigation to establish its role in the aortic aneurysm pathogenesis.
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The activity of transforming growth factor-β in young age with Marfanoid habitus
Pediatrician (St. Petersburg), 2019Co-Authors: Eugene V. Timofeev, Ekaterina Luneva, Eduard Malev, Eduard Zemtsovsky, Тимофеев Евгений Владимирович, Малев Эдуард Геннадьевич, Лунева Екатерина Борисовна, Земцовский Эдуард ВениаминовичAbstract:According to contemporary views, hereditary connective tissue disorders divided classified Marfan syndrome, Loeys-Dietz’s, Ehlers-Danlos syndrome, the primary mitral valve prolapse. It is known that the fibrillinopaty, which include the Marfan syndrome and Loeys-Dietz’s is characterized by activation of TGF-β signaling pathway. With high le vels of TGF-β attributed most of these clinical manifestations these diseases – aneurysm of the aorta, arahnodaktylya, duralectasy. Assessment of the activity of TGF-β in persons with Marfanoid habitus has not previously been studied. Materials and methods . As part of this work, surveyed 70 people: 61 patients young age (median age of 20.1 ± 2.1 years), among which 36 boys and 25 girls and 9 men with verified diagnosis Marfan syndrome (median age 27.9 ± 9.3 years). All survey performed Echocardiography with a targeted search of small anomalies of heart. Results . Correlation analysis showed a direct and reliable connection between arahnodaktylya and concentration of TGF-β1 in serum (r = 0.4, p = 0.05). For young people with signs of Marfanoid habitus are characterized by reliably a higher concentration in the serum of both isoforms of TGF-β. Excess of threshold levels of TGF-β1 revealed at 20% of the core group and not found at all in the control (p < 0.05). Among persons with exceedances of threshold values for at least one faction of the TGF-β patients with signs of Marfanoid habitus met almost three times more often than in the group with normal values of TGF-β (p = 0.01, χ2 = 5.58). In the group of persons with Marfanoid habitus and increases TGF-β are detected more frequently such as atrial septal aneurysm, false chord left ventricle papillary muscles, incremental, deflection of shutters of the mitral valve in 1-2 mm, asymmetry tricuspid aortic valve.
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Cardiomyopathy in patients with Marfan syndrome and Marfanoid habitus
Current Research: Cardiology, 2017Co-Authors: Ekaterina Luneva, Eduard Malev, Alex, Ra Korshunova, Svetlana V. Reeva, Eugeniy Timofeev, Eduard ZemtsovskyAbstract:OBJECTIVES: The term “Marfan cardiomyopathy” is used to indicate changes in left ventricular function in the absence of significant valvular pathology in Marfan syndrome. It is still unknown if there are any changes in cardiac function in patients with similar connective tissue abnormality such as Marfanoid habitus. METHODS: In the study were included 98 persons - 8 patients with Marfan syndrome, 24 with Marfanoid habitus and 66 healthy subjects. Echocardiography was performed to all patients. Speckle tracking echocardiography was used to assess the left ventricular deformation indices. Concentrations of transforming growth factor-β1 and -β2 in serum were determined by enzyme-linked immunosorbent assay. RESULTS: Systolic left ventricular function was significantly lower in the Marfan syndrome group; as well global longitudinal left ventricular strain worsening was detected in MS group comparing to control group. In Marfanoid habitus subjects, we found significant decrease of the circumferential strain in the interventricular septum and inferior wall. transforming growth factor-β1 and -β2 serum levels were elevated in patients with Marfan syndrome. Elevation of transforming growth factor-β1 was statistically nonsignificant unlike to transforming growth factor-β2 in the Marfanoid habitus group. Negative correlations between the serum level of transforming growth factor-β2 and systolic radial strain in the Marfanoid habitus group also have been found. CONCLUSION: Worsening of regional myocardial deformation may be the first sign of deterioration of the left ventricular systolic function and the existence of primary cardiomyopathy in asymptomatic Marfanoid habitus patients, which could affect their long-term prognosis and may be caused by increased transforming growth factor-β signaling.
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Manifestation of cardiomyopathy in patients with Marfan syndrome and Marfanoid habitus
Pediatrician (St. Petersburg), 2016Co-Authors: Ekaterina Luneva, Eduard Malev, Svetlana V. Reeva, Alexandra L Korshunova, Evgeniy V. Timofeev, Eduard ZemtsovskyAbstract:Marfan syndrome is a common genetically determined pathology of connective tissue. It was showed a reduction in systolic and diastolic left ventricular function in patients with Marfan syndrome, as well as the increase in left ventricle size, regardless of previous surgical intervention. Now in literature use the term “cardiomyopathy in Marfan syndrome,” denoting changes of the left ventricular function, in the absence of hemodynamic reasons for its deterioration. In this paper we evaluated the morphological and functional characteristics of the left ventricle, not only in patients with Marfan syndrome, but also in patients with Marfanoid habitus. Materials and methods . The study included 98 people, 8 of them – patients with Marfan syndrome, 24 examinees with Marfanoid habitus and 66 healthy examinees – control group. To all patients entered into the study, echocardiography was performed. Additionally global and local deformation of the myocardium using techniques speckle tracking was assessed. Results significant difference circumferental deformation parameters of the anterior and lateral walls of the left ventricle and its statistically significant reduction in the group with Marfanoid habitus was obtained. Conclusions impaired regional contractility may be the first sign of cardiomyopathy in patients with Marfan syndrome and in such a dysplastic phenotype as Marfanoid habitus that is likely associated with hereditary disorders of the structure and function of connective tissue in various states of dysplastic phenotipes.
Timothy Williams - One of the best experts on this subject based on the ideXlab platform.
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are marfan syndrome and Marfanoid patients distinguishable on long term follow up
The Annals of Thoracic Surgery, 2007Co-Authors: Lars G. Svensson, Eugene H. Blackstone, Jingyuan Feng, Daniel De Oliveira, Maran Thamilarasan, Richard A. Grimm, Brian P. Griffin, Donald Hammer, Marc A Gillinov, Timothy WilliamsAbstract:Background It is unclear whether late outcome differs for Marfan syndrome and Marfanoid patients. Thus, we compared characteristics of Marfan versus Marfanoid patients and their survival and requirement for reoperation. Methods From 1978 to October 2003, 162 patients with a presumptive diagnosis of Marfan syndrome underwent operation. We recategorized them as confirmed Marfan (n = 122), Marfanoid (n = 23), Ehlers-Danlos syndrome (n = 5), or other (n = 12). Patients categorized as Marfanoid failed to meet the major criteria of Marfan syndrome. We compared characteristics of Marfan and Marfanoid groups and assessed long-term survival and need for reoperation. Results Marfan and Marfanoid patients had similar demographics (women, 33% versus 39%; age, 39 ± 13 versus 41 ± 12 years; height, 186 ± 12 cm versus 184 ± 9.6 cm), valve pathophysiology (aortic regurgitation, 66% versus 58%; mitral regurgitation, 58% versus 62%), and aortic pathology (dilated, 40% versus 39%; dissected, 17% versus 13%). Overall hospital survival was 99.3% (144/145), and 10-year survival was similar at 82% in the Marfan and 100% in Marfanoid groups ( p = 0.13). Patients with aortic dissection ( p = 0.001) and mitral valve replacement ( p = 0.003) were at higher risk of death. Reoperation was more frequent after separate aortic valve–ascending aorta graft operations ( p = 0.04), and among taller patients ( p = 0.005). Of 24 Marfan patients with David root reimplantations, none has required reoperation. Conclusions Marfan and Marfanoid patients have similar physical characteristics and postoperative survival, although reoperation was more frequent in Marfan patients. Surgery before occurrence of aortic dissection or mitral valve repair should reduce the risk of reoperation, but taller patients, irrespective of Marfan or gender, are more likely to require reoperation.
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Are Marfan Syndrome and Marfanoid Patients Distinguishable on Long-Term Follow-Up?
The Annals of thoracic surgery, 2007Co-Authors: Lars G. Svensson, Eugene H. Blackstone, Jingyuan Feng, Daniel De Oliveira, A. Marc Gillinov, Maran Thamilarasan, Richard A. Grimm, Brian P. Griffin, Donald Hammer, Timothy WilliamsAbstract:Background It is unclear whether late outcome differs for Marfan syndrome and Marfanoid patients. Thus, we compared characteristics of Marfan versus Marfanoid patients and their survival and requirement for reoperation. Methods From 1978 to October 2003, 162 patients with a presumptive diagnosis of Marfan syndrome underwent operation. We recategorized them as confirmed Marfan (n = 122), Marfanoid (n = 23), Ehlers-Danlos syndrome (n = 5), or other (n = 12). Patients categorized as Marfanoid failed to meet the major criteria of Marfan syndrome. We compared characteristics of Marfan and Marfanoid groups and assessed long-term survival and need for reoperation. Results Marfan and Marfanoid patients had similar demographics (women, 33% versus 39%; age, 39 ± 13 versus 41 ± 12 years; height, 186 ± 12 cm versus 184 ± 9.6 cm), valve pathophysiology (aortic regurgitation, 66% versus 58%; mitral regurgitation, 58% versus 62%), and aortic pathology (dilated, 40% versus 39%; dissected, 17% versus 13%). Overall hospital survival was 99.3% (144/145), and 10-year survival was similar at 82% in the Marfan and 100% in Marfanoid groups ( p = 0.13). Patients with aortic dissection ( p = 0.001) and mitral valve replacement ( p = 0.003) were at higher risk of death. Reoperation was more frequent after separate aortic valve–ascending aorta graft operations ( p = 0.04), and among taller patients ( p = 0.005). Of 24 Marfan patients with David root reimplantations, none has required reoperation. Conclusions Marfan and Marfanoid patients have similar physical characteristics and postoperative survival, although reoperation was more frequent in Marfan patients. Surgery before occurrence of aortic dissection or mitral valve repair should reduce the risk of reoperation, but taller patients, irrespective of Marfan or gender, are more likely to require reoperation.
Eduard Malev - One of the best experts on this subject based on the ideXlab platform.
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P1448 Thoracic aorta and circulating transforming growth factor-b in marfan syndrome and Marfanoid habitus
European Heart Journal - Cardiovascular Imaging, 2020Co-Authors: Eduard Malev, Svetlana V. Reeva, Eugeniy Timofeev, Ekaterina LunevaAbstract:Abstract Purpose Current understanding of the pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MS) focuses upon abnormal activity of the transforming growth factor beta (TGF-β) signalling pathway. Circulating TGF-β predicts cardiovascular events in patients with MS and is elevated in the entire spectrum of aortic syndromes. Marfanoid habitus (MH) patients not meeting the MS criteria (TAA, ectopia lentis, family history), but share the same skeletal features and are the part of the Marfan continuum. Our aim was to evaluate the possible role of elevated TGF-β level in the aortic dilatation at mid-term follow-up in Marfanoid habitus patients. Methods 33 consecutive patients with a presumptive clinical diagnosis of Marfan syndrome were referred to Almazov centre and enrolled in our observational, prospective, single-center study. Nine of them (mean age 27.9 ± 9.3) fulfilled diagnosis of MS according to revised Ghent criteria. 24 subjects (mean age 21.8 ± 3.4) with skeletal features of Marfanoid habitus have had no major findings of MS. Proximal aortic segments were visualized in the parasternal long-axis and suprasternal views. Concentration of TGF-β1 and TGF-β2 in serum was determined using a test system Human Platinum ELISA. End points analyzed during 5 years of follow-up were mortality, aortic-related events, and aortic dimension changes. Results During 122 person-years of the follow-up (median 5.1 years) no deaths or aortic-related events occurred in Marfanoid habitus patients. TGF-β1 and TGF-β2 serum levels were elevated in patients with Marfanoid habitus (14.2 ± 27.6 and 2.1 ± 1.7 ng/ml, respectively) but were lower than in MS group (44.6 ± 47.3 ng/ml, p = 0.03 and 2.7 ± 1.7 ng/ml, p = 0.39, respectively). A high TGF-β1 serum level (cutoff >14.75 ng/ml, provided by the manufacturer of our TGF-β assay) was detected in 44% and TGF-β2 (>2.0 ng/ml) in majority patients (67%) of the MS group. In Marfanoid habitus group we found a high TGF-β1 serum level only in 4 (17%) patients and TGF-β2 in 9 (38%) patients. Aortic diameter at the sinuses of Valsalva and Z-score were significantly lower in Marfanoid habitus group (29.2 ± 2.8 mm and 1.56 ± 0.93) than in MS patients (43.1 ± 15.1 mm, p = 0.0007 and 6.86 ± 5.83, p = 0.004) at the beginning of study and significantly increased during the follow-up (31.3 ± 2.9 mm and 1,69 ± 0,15, p < 0.001 for both). There was no correlation between TGF-β level and aortic dimensions in patients with MS and Marfanoid habitus. Conclusion In young adults with Marfanoid habitus and the current absence of ascending aortic aneurysm we found the increased TGF-β level and aortic root enlargement during the follow-up. High TGF-β serum level may contribute to the excessive progression of aortic dilatation later over mid-to-late aging and requires further investigation to establish its role in the aortic aneurysm pathogenesis.
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The activity of transforming growth factor-β in young age with Marfanoid habitus
Pediatrician (St. Petersburg), 2019Co-Authors: Eugene V. Timofeev, Ekaterina Luneva, Eduard Malev, Eduard Zemtsovsky, Тимофеев Евгений Владимирович, Малев Эдуард Геннадьевич, Лунева Екатерина Борисовна, Земцовский Эдуард ВениаминовичAbstract:According to contemporary views, hereditary connective tissue disorders divided classified Marfan syndrome, Loeys-Dietz’s, Ehlers-Danlos syndrome, the primary mitral valve prolapse. It is known that the fibrillinopaty, which include the Marfan syndrome and Loeys-Dietz’s is characterized by activation of TGF-β signaling pathway. With high le vels of TGF-β attributed most of these clinical manifestations these diseases – aneurysm of the aorta, arahnodaktylya, duralectasy. Assessment of the activity of TGF-β in persons with Marfanoid habitus has not previously been studied. Materials and methods . As part of this work, surveyed 70 people: 61 patients young age (median age of 20.1 ± 2.1 years), among which 36 boys and 25 girls and 9 men with verified diagnosis Marfan syndrome (median age 27.9 ± 9.3 years). All survey performed Echocardiography with a targeted search of small anomalies of heart. Results . Correlation analysis showed a direct and reliable connection between arahnodaktylya and concentration of TGF-β1 in serum (r = 0.4, p = 0.05). For young people with signs of Marfanoid habitus are characterized by reliably a higher concentration in the serum of both isoforms of TGF-β. Excess of threshold levels of TGF-β1 revealed at 20% of the core group and not found at all in the control (p < 0.05). Among persons with exceedances of threshold values for at least one faction of the TGF-β patients with signs of Marfanoid habitus met almost three times more often than in the group with normal values of TGF-β (p = 0.01, χ2 = 5.58). In the group of persons with Marfanoid habitus and increases TGF-β are detected more frequently such as atrial septal aneurysm, false chord left ventricle papillary muscles, incremental, deflection of shutters of the mitral valve in 1-2 mm, asymmetry tricuspid aortic valve.
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A Marfanoid Habitus Dyagnostics’ Algorithm And Morfo-Functional Heart Singularities Relevent To This Dysplastic Phenotype
Pediatrician (St. Petersburg), 2017Co-Authors: Evgenij V Timofeev, Eduard Malev, Bajazit I Zaripov, Eduard ZemtsovskyAbstract:Official Russian guidelines for inherited connective tissue diseases distinguish a range of dysplastic phenotypes, with the Marfanoid habitus being one of them. The prevalence of the Marfanoid habitus and morfometrical heart singularities among the young practically healthy persons were not studied before. Materials and methods of the study: 560 practically healthy young persons aged from 18 to 25 years (average value 19.2 ± 1.4) were examined within the framework of the study. All the persons were subjected to phenotypical and anthropometrical examinations, with a group of 320 persons studied with the Echo-cardiographic procedure specifically aimed at small heart anomalies’ discovery. The study resulted in assessment of the Marfanoid habitus among the young persons depending on sex and selected threshold of Dolichostenomelia and arachnodactylia coefficients. It shows that the use of the diagnostic algorithms offered by official Russian recommendations leads to the identification of this state of nearly half practically healthy young male persons. This could cause a hyper-diagnostics among this contingent group. The girls with Marfanoid habitus demonstrate alternated morfometrical parameters - greater myocardia mass index, bigger thickness of myocardia, the trend to left cardiac ventricle hypertrophy. The persons with Marfanoid habitus also tend to have some cardiac anomalies more frequently (mitral and tricuspidal valve prolapsed, left ventricular false tendons, foramen ovale).
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Cardiomyopathy in patients with Marfan syndrome and Marfanoid habitus
Current Research: Cardiology, 2017Co-Authors: Ekaterina Luneva, Eduard Malev, Alex, Ra Korshunova, Svetlana V. Reeva, Eugeniy Timofeev, Eduard ZemtsovskyAbstract:OBJECTIVES: The term “Marfan cardiomyopathy” is used to indicate changes in left ventricular function in the absence of significant valvular pathology in Marfan syndrome. It is still unknown if there are any changes in cardiac function in patients with similar connective tissue abnormality such as Marfanoid habitus. METHODS: In the study were included 98 persons - 8 patients with Marfan syndrome, 24 with Marfanoid habitus and 66 healthy subjects. Echocardiography was performed to all patients. Speckle tracking echocardiography was used to assess the left ventricular deformation indices. Concentrations of transforming growth factor-β1 and -β2 in serum were determined by enzyme-linked immunosorbent assay. RESULTS: Systolic left ventricular function was significantly lower in the Marfan syndrome group; as well global longitudinal left ventricular strain worsening was detected in MS group comparing to control group. In Marfanoid habitus subjects, we found significant decrease of the circumferential strain in the interventricular septum and inferior wall. transforming growth factor-β1 and -β2 serum levels were elevated in patients with Marfan syndrome. Elevation of transforming growth factor-β1 was statistically nonsignificant unlike to transforming growth factor-β2 in the Marfanoid habitus group. Negative correlations between the serum level of transforming growth factor-β2 and systolic radial strain in the Marfanoid habitus group also have been found. CONCLUSION: Worsening of regional myocardial deformation may be the first sign of deterioration of the left ventricular systolic function and the existence of primary cardiomyopathy in asymptomatic Marfanoid habitus patients, which could affect their long-term prognosis and may be caused by increased transforming growth factor-β signaling.
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Manifestation of cardiomyopathy in patients with Marfan syndrome and Marfanoid habitus
Pediatrician (St. Petersburg), 2016Co-Authors: Ekaterina Luneva, Eduard Malev, Svetlana V. Reeva, Alexandra L Korshunova, Evgeniy V. Timofeev, Eduard ZemtsovskyAbstract:Marfan syndrome is a common genetically determined pathology of connective tissue. It was showed a reduction in systolic and diastolic left ventricular function in patients with Marfan syndrome, as well as the increase in left ventricle size, regardless of previous surgical intervention. Now in literature use the term “cardiomyopathy in Marfan syndrome,” denoting changes of the left ventricular function, in the absence of hemodynamic reasons for its deterioration. In this paper we evaluated the morphological and functional characteristics of the left ventricle, not only in patients with Marfan syndrome, but also in patients with Marfanoid habitus. Materials and methods . The study included 98 people, 8 of them – patients with Marfan syndrome, 24 examinees with Marfanoid habitus and 66 healthy examinees – control group. To all patients entered into the study, echocardiography was performed. Additionally global and local deformation of the myocardium using techniques speckle tracking was assessed. Results significant difference circumferental deformation parameters of the anterior and lateral walls of the left ventricle and its statistically significant reduction in the group with Marfanoid habitus was obtained. Conclusions impaired regional contractility may be the first sign of cardiomyopathy in patients with Marfan syndrome and in such a dysplastic phenotype as Marfanoid habitus that is likely associated with hereditary disorders of the structure and function of connective tissue in various states of dysplastic phenotipes.
Keiko Shimojima - One of the best experts on this subject based on the ideXlab platform.
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Marfanoid hypermobility caused by an 862 kb deletion of Xq22.3 in a patient with Sotos syndrome.
American journal of medical genetics. Part A, 2011Co-Authors: Keiko Shimojima, Tohru Okanishi, Toshiyuki YamamotoAbstract:Sotos syndrome is a rare genetic disorder characterized by overgrowth associated with macrocephaly and delayed psychomotor development. Patients with Sotos syndrome show 5q35 deletions involving NSD1 or its point mutations. We identified the common 5q35 deletion in a patient with atypical Sotos syndrome manifesting extremely severe developmental delay, joint hypermobility, and skin hyperextensibility, which are recognized as Marfanoid hypermobility syndrome. Further analyses were performed to identify the genetic cause of these additional findings. aCGH analysis revealed an additional 862 kb deletion of Xq22.3 in this patient, which was inherited from his healthy mother. The deleted region included five genes, including the nik-related kinase gene (NRK), which would be a candidate gene for the patient's Marfanoid hypermobility, because it is a member of the glucokinase subfamily that are involved in activating the JNK pathway, and is expressed in developing skeletal musculature. Severe developmental delay seen in the patient may be derived from position effect of the deletion for neighboring interleukin 1 receptor accessory protein-like 2 gene (IL1RAPL2), which is a candidate gene for X-linked mental retardation.
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Marfanoid hypermobility caused by an 862 kb deletion of Xq22.3 in a patient with Sotos syndrome.
American Journal of Medical Genetics Part A, 2011Co-Authors: Keiko Shimojima, Tohru Okanishi, Toshiyuki YamamotoAbstract:Sotos syndrome is a rare genetic disorder characterized by overgrowth associated with macrocephaly and delayed psychomotor development. Patients with Sotos syndrome show 5q35 deletions involving NSD1 or its point mutations. We identified the common 5q35 deletion in a patient with atypical Sotos syndrome manifesting extremely severe developmental delay, joint hypermobility, and skin hyperextensibility, which are recognized as Marfanoid hypermobility syndrome. Further analyses were performed to identify the genetic cause of these additional findings. aCGH analysis revealed an additional 862 kb deletion of Xq22.3 in this patient, which was inherited from his healthy mother. The deleted region included five genes, including the nik-related kinase gene (NRK), which would be a candidate gene for the patient's Marfanoid hypermobility, because it is a member of the glucokinase subfamily that are involved in activating the JNK pathway, and is expressed in developing skeletal musculature. Severe developmental delay seen in the patient may be derived from position effect of the deletion for neighboring interleukin 1 receptor accessory protein-like 2 gene (IL1RAPL2), which is a candidate gene for X-linked mental retardation. © 2011 Wiley-Liss, Inc.