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Cureus Feb 2024Marfan syndrome (MFS) presents complex cardiovascular manifestations and challenges in management due to its impact on multiple body systems. This case study examines...
Marfan syndrome (MFS) presents complex cardiovascular manifestations and challenges in management due to its impact on multiple body systems. This case study examines the clinical profile, diagnostic findings, and physiotherapy intervention for a 57-year-old male with MFS who experienced severe aortic and mitral valvular complications. The patient's admission was marked by fatigue, reduced mobility, breathlessness, and a confirmed diagnosis of MFS. Cardiac evaluation revealed severe regurgitation and aortic root dilation. The patient's symptoms were exhaustion, giddiness, dyspnea, and decreased mobility. The objective of this case study was to describe the impact of graded mobilization and pacing techniques in maximizing functional mobility and alleviating symptoms associated with aortic regurgitation and aortic root dilatation through an extensive physiotherapy program. Exercises addressing dyspnea, lung capacity, posture, functional mobility, and fatigue reduction were included in the physiotherapy intervention. The rehabilitation outcome showed a notable shift of score from 3 to 0.5 on the Borg scale of dyspnea, indicating enhanced functional capacity and improved quality of life. Post-rehabilitation, the patient exhibited significant progress in the two-minute walk test. This case highlights the importance of tailored interventions in managing MFS-related cardiac complications.
PubMed: 38524030
DOI: 10.7759/cureus.54591 -
Archivos de Cardiologia de Mexico 2024Ascending aortic aneurysms are rare pathologies in childhood, especially in the absence of previous diseases such as Marfan syndrome.
BACKGROUND
Ascending aortic aneurysms are rare pathologies in childhood, especially in the absence of previous diseases such as Marfan syndrome.
OBJECTIVE
Present the possibility of successful endovascular management of large vessel aneurysms, using stents and microcatheters with embolization of the aneurysm sac.
METHOD
We present the case of a previously healthy ten-year-old patient, in whom a pseudoaneurysm was documented between the origin of the left common carotid artery and left subclavian artery, successfully managed endovascularly, initially with a stent covering the neck of the aneurysm to remodel it and later with embolization of the aneurysm sac using a microcatheter.
RESULTS
Aneurysms of large vessels, such common carotid artery and subclavian artery, are at risk of rupture with devastating complications; endovascular management is considered a minimally invasive management option, with favorable results.
CONCLUSION
The endovascular management of large vessel aneurysms using stents and microcatheters with embolization of the aneurysmal sac is a novel management option that achieves successful results.
Topics: Humans; Child; Aneurysm, Aortic Arch; Aortic Aneurysm; Stents; Aneurysm, False; Treatment Outcome; Endovascular Procedures; Aortic Aneurysm, Thoracic
PubMed: 38507313
DOI: 10.24875/ACM.22000272 -
Translational Vision Science &... Mar 2024To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data.
PURPOSE
To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data.
METHODS
Diagnostic standards (Ghent nosology) and genetic test were applied in all patients with CEL to determine the presence or absence of MFS. Three potential MFS predictors were tested and chosen to build a prediction model using logistic regression. The predictive performance of the nomogram was validated internally through time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis.
RESULTS
Eyes from 103 patients under 20 years old and with CEL were enrolled in this study. Z score of body mass index (odds ratio [OR] = 0.659; 95% confidence interval [CI], 0.453-0.958), corneal curvature radius (OR = 3.397; 95% CI, 1.829-6.307), and aortic root diameter (OR = 2.342; 95% CI, 1.403-3.911) were identified as predictors of MFS. The combination of the above predictors shows good predictive ability, as indicated by area under the curve of 0.889 (95% CI, 0.826-0.953). The calibration curves showed good agreement between the prediction of the nomogram and the actual observations. In addition, decision curve analysis showed that the nomogram was clinically useful and had better discriminatory power in identifying patients with MFS. For better individual prediction, an online MFS calculator was created.
CONCLUSIONS
The nomogram provides accurate and individualized prediction of MFS in children with CEL who cannot be identified with the Ghent criteria, enabling clinicians to personalize treatment plans and improve MFS outcomes.
TRANSLATIONAL RELEVANCE
The prediction model may help clinicians identify MFS in its early stages, which could reduce the likelihood of developing severe symptoms and improve MFS outcomes.
Topics: Child; Humans; Young Adult; Adult; Ectopia Lentis; Marfan Syndrome; Nomograms; Eye
PubMed: 38502141
DOI: 10.1167/tvst.13.3.15 -
Research Square Mar 2024We performed a secondary analysis of the Pediatric Heart Network Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and...
We performed a secondary analysis of the Pediatric Heart Network Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and aortic phenotypes in study participants. Aortic aneurysm phenotype was defined as aortic root Z-score ≥ 4.5, aortic root growth rate ≥ 75th percentile, aortic dissection, and aortic surgery. Severe cardiac phenotype was defined as aortic dissection, aortic Z-score ≥4.5, aortic valve surgery, at least moderate mitral regurgitation, mitral valve surgery, left ventricular dysfunction, or death. Extracardiac manifestations were characterized by specific organ system involvement and by a novel aggregate extracardiac score that was created for this study based on the original Ghent nosology. Logistic regression analysis compared aggregate extracardiac score and systems involvement to outcomes. Of 608 participants (60% male), the median age at enrollment was 10.8 years (interquartile range: 6, 15.4). Aortic aneurysm phenotype was observed in 71% of participants and 64% had severe cardiac phenotype. On univariate analysis, skeletal (OR: 1.95, 95% CI: 1.01, 3.72; p = 0.05), skin manifestation (OR: 1.62, 95% CI: 1.13, 2.34; p = 0.01) and aggregate extracardiac score (OR: 1.17, 95% CI: 1.02, 1.34; p = 0.02) were associated with aortic aneurysm phenotype but were not significant in multivariate analysis. There was no association between extracardiac manifestations and severe cardiac phenotype. Thus, the severity of cardiac manifestations in Marfan syndrome was independent of extracardiac phenotype and aggregate extracardiac score. Severity of extracardiac involvement did not appear to be a useful clinical marker for cardiovascular risk-stratification in this cohort of children and young adults with Marfan syndrome.
PubMed: 38496659
DOI: 10.21203/rs.3.rs-3994693/v1 -
Methodist DeBakey Cardiovascular Journal 2024Thoracic aortic disease (TAD) poses substantial risks during pregnancy, particularly for women with genetic conditions such as Marfan syndrome, Loeys-Dietz syndrome, and... (Review)
Review
Thoracic aortic disease (TAD) poses substantial risks during pregnancy, particularly for women with genetic conditions such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome. This review examines the epidemiology, risk assessment, and management of TAD in pregnancy. Preconception counseling is vital considering the hereditary nature of TAD and potential pregnancy-related complications. Genetic testing and imaging surveillance aid in risk assessment. Medical management, including beta-blockade and strict blood pressure control, is essential throughout pregnancy. Surgical interventions may be necessary in certain cases. A multidisciplinary approach involving cardiologists, obstetricians, cardiac surgeons, anesthesiologists, and other specialists with expertise in cardio-obstetrics is essential for optimal outcomes. Patient education and shared decision-making play vital roles in navigating the complexities of TAD in pregnancy and improving maternal and neonatal outcomes.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Aortic Diseases; Aorta; Loeys-Dietz Syndrome; Marfan Syndrome; Risk Assessment
PubMed: 38495666
DOI: 10.14797/mdcvj.1371 -
Cureus Feb 2024Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural... (Review)
Review
Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural valvular abnormalities as cardiovascular involvement has been identified as the most life-threatening aspect of the syndrome. This was a systematic review with a meta-analysis of studies indexed in Medline from the inception of the database to November 7, 2022. Using the random-effects model, separate Forest and Galbraith plots were generated for each valvular abnormality assessed. Heterogeneity was assessed using the statistics whilst funnel plots and Egger's test were used to assess for publication bias. From a total of 35 studies, a random-effects meta-analysis approximated the pooled summary estimates for the prevalence of cardiac valve abnormalities as mitral valve prolapse 65% (95% CI: 57%-73%); mitral valve regurgitation 40% (95% CI: 29%-51%); aortic valve regurgitation 40% (95% CI: 28%-53%); tricuspid valve prolapse 35% (95% CI: 15%-55%); and tricuspid valve regurgitation 43% (95% CI: 8%-78%). Only one study reported on the involvement of the pulmonary valve (pulmonary valve prolapse was estimated at 5.3% (95% CI: 1.9%-11.1%) in a cohort of 114 patients with MFS). We believe this study provides a description of the structural valvular disease spectrum and may help inform providers and patients in understanding the clinical history of MFS in the current treatment era with its increased life expectancy.
PubMed: 38487153
DOI: 10.7759/cureus.54141 -
International Journal of Molecular... Feb 2024Mutations of the gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is...
Mutations of the gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction. Furthermore, we incubated the SMCs with Coenzyme Q10 (CoQ10) to assess whether restoring mitochondrial function can reverse the phenotypic transformation. The results showed that SMCs had decreased (mitochondrial transcription factor A), mtDNA levels and mitochondrial mass, lost their contractile capacity and had increased synthetic phenotype markers. Inhibiting the mitochondrial function of SMCs can decrease the expression of contractile markers and increase the expression of synthetic genes. Imposing mitochondrial stress causes a double-hit effect on the level, oxidative phosphorylation and phenotypic transformation of -knockdown SMCs while restoring mitochondrial metabolism with CoQ10 can rapidly reverse the synthetic phenotype. Our results suggest that mitochondria function is a potential therapeutic target for the phenotypic transformation of SMCs in MFS.
Topics: Humans; Marfan Syndrome; Phenotype; Myocytes, Smooth Muscle; Mitochondrial Diseases; Fibrillin-1; Adipokines; Ubiquinone
PubMed: 38473909
DOI: 10.3390/ijms25052662 -
International Journal of Molecular... Feb 2024Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms... (Review)
Review
Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) exhibit differences and similarities in their pathophysiological and pathogenetic features. AAA is a multifactorial disease, mainly associated with atherosclerosis, characterized by a relevant inflammatory response and calcification. TAA is rarely associated with atherosclerosis and in some cases is associated with genetic mutations such as Marfan syndrome (MFS) and bicuspid aortic valve (BAV). MFS-related and non-genetic or sporadic TAA share aortic degeneration with endothelial-to-mesenchymal transition (End-Mt) and fibrosis, whereas in BAV TAA, aortic degeneration with calcification prevails. microRNA (miRNAs) contribute to the regulation of aneurysmatic aortic remodeling. miRNAs are a class of non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report the involvement of deregulated miRNAs in the different aortic remodeling characterizing AAAs and TAAs. In AAA, miRNA deregulation appears to be involved in parietal inflammatory response, smooth muscle cell (SMC) apoptosis and aortic wall calcification. In sporadic and MFS-related TAA, miRNA deregulation promotes End-Mt, SMC myofibroblastic phenotypic switching and fibrosis with glycosaminoglycan accumulation. In BAV TAA, miRNA deregulation sustains aortic calcification. Those differences may support the development of more personalized therapeutic approaches.
Topics: Humans; Aortic Valve; MicroRNAs; Aortic Aneurysm; Aortic Aneurysm, Thoracic; Bicuspid Aortic Valve Disease; Marfan Syndrome; Calcinosis; Phenotype; Atherosclerosis; Fibrosis
PubMed: 38473887
DOI: 10.3390/ijms25052641 -
European Journal of Pediatrics May 2024Children with Marfan (MFS) and Loeys-Dietz syndrome (LDS) report limitations in physical activities, sports, school, leisure, and work participation in daily life. This... (Observational Study)
Observational Study
Children with Marfan (MFS) and Loeys-Dietz syndrome (LDS) report limitations in physical activities, sports, school, leisure, and work participation in daily life. This observational, cross-sectional, multicenter study explores associations between physical fitness and cardiovascular parameters, systemic manifestations, fatigue, and pain in children with MFS and LDS. Forty-two participants, aged 6-18 years (mean (SD) 11.5(3.7)), diagnosed with MFS (n = 36) or LDS (n = 6), were enrolled. Physical fitness was evaluated using the Fitkids Treadmill Test's time to exhaustion (TTE) outcome measure. Cardiovascular parameters (e.g., echocardiographic parameters, aortic surgery, cardiovascular medication) and systemic manifestations (systemic score of the revised Ghent criteria) were collected. Pain was obtained by visual analog scale. Fatigue was evaluated by PROMIS® Fatigue-10a-Pediatric-v2.0-short-form and PROMIS® Fatigue-10a-Parent-Proxy-v2.0-short-form. Multivariate linear regression analyses explored associations between physical fitness (dependent variable) and independent variables that emerged from the univariate linear regression analyses (criterion p < .05). The total group (MFS and LDS) and the MFS subgroup scored below norms on physical fitness TTE Z-score (mean (SD) -3.1 (2.9); -3.0 (3.0), respectively). Univariate analyses showed associations between TTE Z-score aortic surgery, fatigue, and pain (criterion p < .05). Multivariate analyses showed an association between physical fitness and pediatric self-reported fatigue that explained 48%; 49%, respectively, of TTE Z-score variance (F (1,18) = 18.6, p ≤ .001, r = .48; F (1,15) = 16,3, p = .01, r = .49, respectively). Conclusions: Physical fitness is low in children with MFS or LDS and associated with self-reported fatigue. Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with MFS and LDS. What is Known: • Marfan and Loeys-Dietz syndrome are heritable connective tissue disorders and share cardiovascular and systemic manifestations. • Children with Marfan and Loeys-Dietz syndrome report increased levels of disability, fatigue and pain, as well as reduced levels of physical activity, overall health and health-related quality of life. What is New: • Physical fitness is low in children with Marfan and Loeys-Dietz syndrome and associated with self-reported fatigue. • Our findings emphasize the potential of standardized and tailored exercise programs to improve physical fitness and reduce fatigue, ultimately enhancing the physical activity and sports, school, leisure, and work participation of children with Marfan and Loeys-Dietz syndrome.
Topics: Humans; Loeys-Dietz Syndrome; Adolescent; Marfan Syndrome; Child; Male; Cross-Sectional Studies; Female; Physical Fitness; Fatigue; Pain; Exercise Test
PubMed: 38466415
DOI: 10.1007/s00431-024-05456-z -
Scientific Reports Mar 2024In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS...
In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS (Fbn1) has been advantageous in investigating MFS-associated life-threatening aortic aneurysms. It is well established that the MFS mouse model exhibits an accelerated-aging phenotype in elastic organs like the aorta, lung, and skin. However, the impact of Fbn1 mutations on the in vivo function and structure of various artery types with the consideration of sex and age, has not been adequately explored in real-time and a clinically relevant context. In this study, we investigate if Fbn1 mutation contributes to sex-dependent alterations in central and cerebral vascular function similar to phenotypic changes associated with normal aging in healthy control mice. In vivo ultrasound imaging of central and cerebral vasculature was performed in 6-month-old male and female MFS and C57BL/6 mice and sex-matched 12-month-old (middle-aged) healthy control mice. Our findings confirm aortic enlargement (aneurysm) and wall stiffness in MFS mice, but with exacerbation in male diameters. Coronary artery blood flow velocity (BFV) in diastole was not different but left pulmonary artery BFV was decreased in MFS and 12-month-old control mice regardless of sex. At 6 months of age, MFS male mice show decreased posterior cerebral artery BFV as compared to age-matched control males, with no difference observed between female cohorts. Reduced mitral valve early-filling velocities were indicated in MFS mice regardless of sex. Male MFS mice also demonstrated left ventricular hypertrophy. Overall, these results underscore the significance of biological sex in vascular function and structure in MFS mice, while highlighting a trend of pre-mature vascular aging phenotype in MFS mice that is comparable to phenotypes observed in older healthy controls. Furthermore, this research is a vital step in understanding MFS's broader implications and sets the stage for more in-depth future analyses, while providing data-driven preclinical justification for re-evaluating diagnostic approaches and therapeutic efficacy.
Topics: Animals; Female; Male; Mice; Aorta; Fibrillin-1; Marfan Syndrome; Mice, Inbred C57BL; Mutation; Phenotype
PubMed: 38461168
DOI: 10.1038/s41598-024-56438-y