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In recent years, there have been many advances in the treatment of cardiac disease in children with Marfan's syndrome. Early diagnosis, meticulous echocardiographic follow-up and multidisciplinary assessment are essential. Medical treatment with beta-blockers is probably helpful in most children with aortic root dilatation. Research on TGFbeta sign...
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Citations
... 28 The most common cardiovascular manifestations of MS include: aortic root dilatation, pulmonary artery dilatation and MVP. 29 Several musculoskeletal abnormalities may be observed in MS patients, particularly 'wrist sign,' 'thumb sign,' PC deformity, PE or chest asymmetry, hindfoot deformity, severe flatfoot, dural ectasia, protrusio acetabuli, reduced upper segment/lower segment and increased arm span-height ratio, scoliosis and kyphosis. PE is the most common skeletal abnormality detected in MS patients, occurring in two-thirds of them, 30 with an unclear etiopathogenesis. ...
Background
Literature data suggest high inter-study variability in mitral valve prolapse (MVP) prevalence among individuals with thoracic skeletal abnormalities (TSA). This systematic review aimed at estimating the overall prevalence of MVP in individuals with the most common TSA, including not only the oldest studies (before the year 2000) but also the most recent ones (after the year 2000).
Methods
PubMed and EMBASE databases were systematically reviewed in November 2023. Studies assessing the relationship between MVP and TSA and estimating the MVP prevalence in pectus excavatum (PE), pectus carinatum (PC), scoliosis, straight back syndrome (SBS) and Marfan syndrome (MS) were included. There was no limitation on time periods.
Results
Twenty-five studies with a total of 2800 patients (27.9 ± 13.9 years, 48.2% females) were analyzed. The highest prevalence of MVP was observed among MS patients (47.3%), while the lowest was detected in PC individuals (23%). Prevalence of MVP was similar among PE (30.8%), scoliosis (26.3%) and SBS (25.5%) patients. When dividing the studies on the basis of temporal period, the average MVP prevalence was approximately two-fold higher in all studies conducted before the year 2000 in comparison with the most recent ones, regardless of TSA type. This discrepancy might be primarily ascribed to relevant differences in the echocardiographic criteria employed for MVP diagnosis before (less specific) and after (more specific) the year 2000, respectively.
Conclusions
The estimated MVP prevalence in TSA individuals is significantly higher than that observed in the general population. Individuals with TSA should be screened for MVP presence on transthoracic echocardiography.
... In addition, it has been demonstrated that as the degree of FPP increases, the risk of concomitant MVP also increases [8]. Furthermore, in connective tissue disorders characterized by hypermobility such as Marfan syndrome and Ehler-Danlos syndrome, cardiac pathologies can also be encountered [9,10]. ...
Objective: The aim of this study is to investigate the relationship between flexible pes planus (FPP) and cardiac pathologies in pediatric patients, with a particular emphasis on hypermobility status.
Methods: Between January and June 2022, a retrospective screening was conducted on a total of 68 patients aged between 6 and 18 years who had been diagnosed with FPP. Eight patients were excluded from the study due to suspicion of connective tissue or neuromuscular diseases following systemic examinations conducted by a pediatric specialist. The included 60 patients underwent comprehensive cardiac examinations conducted by pediatric cardiology specialists and were evaluated through echocardiography (ECHO) as part of the study. Simultaneously, a control group of healthy individuals aged 6 to 18, without a diagnosis of pes planus (PP), was selected from those who applied for health reports for the purpose of obtaining sports licenses. Patients diagnosed with FPP were compared to a control group in terms of the presence of cardiac pathology. Furthermore, the Beighton Hypermobility Scores (BHSs) of patients diagnosed with FPP were compared based on the presence of cardiac pathology.
Results: A total of 60 patients (40 males, 20 females) diagnosed with FPP were included in the study, and a control group consisting of 453 healthy individuals (287 males, 166 females) was selected. The incidence of cardiac pathology in patients diagnosed with FPP (23.3%) was found to be significantly higher compared to the control group (7%) (p <0.01). The risk of cardiac pathology in patients diagnosed with FPP was determined to be four times higher compared to the control group (Odds ratio: 4 (1.993-8.046), p<0.01). Among patients with FPP, individuals who were found to have cardiac pathology had statistically significantly higher average BHSs compared to those without cardiac pathology (p: 0.043).
Conclusions: Our study suggested that there may be a significant relationship between FPP and high cardiac pathology risk in pediatric patients. We observed a significant increase in the incidence of cardiac pathologies among patients diagnosed with FPP. Additionally, the presence of higher hypermobility scores among patients diagnosed with FPP suggests a potential connection between the two. In the evaluation of FPP in the pediatric population, it should be considered as a potential risk factor for cardiac pathologies and its potential association with hypermobility.
... Aortic Elongation is a medical condition in which the aorta, the largest artery in the human body, is longer than normal [1]. This can occur for various reasons, including age-associated changes [2], congenital factors [10,3,6,15,5], or underlying medical conditions that affect the elasticity of blood vessels, resulting in Cardiovascular Diseases (CVD). Common diseases associated to aortic elongation include aortic aneurysms [9], Marfan Syndrome [10], Ehlers-Danlos Syndrome [3], Loeys-Dietz Syndrome [15] and Turner Syndrome [5]. ...
... This can occur for various reasons, including age-associated changes [2], congenital factors [10,3,6,15,5], or underlying medical conditions that affect the elasticity of blood vessels, resulting in Cardiovascular Diseases (CVD). Common diseases associated to aortic elongation include aortic aneurysms [9], Marfan Syndrome [10], Ehlers-Danlos Syndrome [3], Loeys-Dietz Syndrome [15] and Turner Syndrome [5]. The consequences of an elongated aorta can vary depending on the severity and cause of the condition. ...
Aortic Elongation can result from age-related changes, congenital factors, aneurysms, or conditions affecting blood vessel elasticity. It is associated with cardiovascular diseases and severe complications like aortic aneurysms and dissection. In this
work, we evaluated the performance of deep learning models (DenseNet and EfficientNet) for aortic elongation detection based on transfer learning and fine-tunning techniques using Chest X-Rays (CXR) as input. DenseNet achieved higher accuracy (84.7% ± 0.7), precision (75.6% ± 1.3), sensitivity (88.7% ± 2.7), specificity (82.3% ± 1.6), F1-score (81.6% ± 1.0), and AUROC (93.1% ± 0.4) than EfficientNet. To gain insights into the decision-making process of the deep learning models, we employed Grad-CAM and LIME explainability methods. Through these techniques, we were able to successfully identify the expected location of aortic elongation in the x-ray images. Moreover, we used the pixel-flipping method to assess quantitatively the interpretations providing valuable insights into models behavior. By incorporating explainable AI techniques, we enhanced the interpretability and understanding of the models' decisions. This approach holds promise for aiding clinicians in timely and accurate diagnosis, potentially improving patient outcomes in clinical practice.
... Chronic inflammation of the aortic wall and, in some cases extending to the periaortic space are conditions called aortitis and periaortitis, respectively. Aortitis is associated with inflammatory damage to the elastic properties and tissue oedema [14] -of all three layers of aortic wall. It can affect any part of the aorta and expand through the larger vessels. ...
Thoracic Aortic Aneurysm pertains to the segment of the aortic organ with a weakened wall resulting in dilation or even rupture. Through many years of research, this condition is now associated widely with mutations of specific genes- most significantly, FBN1 and TGFBR1/TGFBR2 genes resulting in Marfan Syndrome and Loeys-Dietz Syndrome, respectively. These mutations were found to affect the degree of clinical manifestations and the decision on aortic surgery. In this review, we discussed the effect of genetic markers on aortic aneurysms and their importance in the modern world when considering primary prevention, prophylactic treatment, and counseling of both patients and their families.
... Remarkably, the inheritance of several conditions should also be faced. Heredity is expected to manifest in 50% of patients with genetic disorders associated with cCHD, such as DiGeorge (22q11 deletion) (24, 25), Marfan (26), Heart-hand syndromes (26,27) Holt-Oram (28), Nooman (29), Alagille (30), CHARGE (31), Williams-Beuren (32), Cutis laxa (33), Vascular Ehlers-Danlos (vED) (34), and Silver-Russel syndromes (35). Several scores have been proposed to assess risk in pregnant women or those planning pregnancy. ...
Significant maternal and fetal morbidity and mortality risk has been shown to be associated with cardiovascular disease in pregnancy. Several determinants, such as the increasing number of females with corrected congenital heart disease in reproductive age, a more advanced maternal age associated with cardiovascular risk factors, and a greater prevalence of preexisting comorbidities related to cardiac disorders such as cancer and COVID-19), lead to a higher incidence of cardiac complications in pregnancy in the last few decades. However, adopting a multidisciplinary strategy may influence maternal and neonatal outcomes. This review aims at assessing the role of the Pregnancy Heart Team, which should ensure careful pre-pregnancy counseling, pregnancy monitoring, and delivery planning for both congenital and other cardiac or metabolic disorders, addressing several emerging aspects in the multidisciplinary team-based approach.
... In the absence of a formal diagnosis, the management of individuals with features of Marfan syndrome (including cases with ectopia lentis, even when this is apparently/presumably isolated) should be approached with caution. For example, there are general anaesthetic considerations that may affect surgical planning in Marfan syndrome suspects [20][21][22]. Additionally, regular monitoring/screening is indicated, and this has been shown to contribute significantly to the burden of care experienced by affected individuals [23]. ...
... In the absence of a formal diagnosis, the management of individua with features of Marfan syndrome (including cases with ectopia lentis, even when this apparently/presumably isolated) should be approached with caution. For example, ther are general anaesthetic considerations that may affect surgical planning in Marfan syn drome suspects [20][21][22]. Additionally, regular monitoring/screening is indicated, and th has been shown to contribute significantly to the burden of care experienced by affecte individuals [23]. ...
Non-traumatic ectopia lentis can be isolated or herald an underlying multisystemic disorder. Technological advances have revolutionized genetic testing for many ophthalmic disorders, and this study aims to provide insights into the clinical utility of genetic analysis in paediatric ectopia lentis. Children that underwent lens extraction for ectopia lentis between 2013 and 2017 were identified, and gene panel testing findings and surgical outcomes were collected. Overall, 10/11 cases received a probable molecular diagnosis. Genetic variants were identified in four genes: FBN1 (associated with Marfan syndrome and cardiovascular complications; n = 6), ADAMTSL4 (associated with non-syndromic ectopia lentis; n = 2), LTBP2 (n = 1) and ASPH (n = 1). Parents appeared unaffected in 6/11 cases; the initial presentation of all six of these children was to an ophthalmologist, and only 2/6 had FBN1 variants. Notably, 4/11 cases required surgery before the age of 4 years, and only one of these children carried an FBN1 variant. In summary, in this retrospective cohort study, panel-based genetic testing pointed to a molecular diagnosis in >90% of paediatric ectopia lentis cases requiring surgery. In a subset of study participants, genetic analysis revealed changes in genes that have not been linked to extraocular manifestations and highlighted that extensive systemic investigations were not required in these individuals. We propose the introduction of genetic testing early in the diagnostic pathway in children with ectopia lentis.
... The majority of adults with MFS have an abnormal cardiovascular system. The most common abnormalities are aortic regurgitation and aorta dilation, which occur in 60-80% of patients and can lead to aortic dissection as a complication [7]. Moreover, children with MFS are assessed for cardiac abnormalities using echocardiography, which includes a full study of the ventricles, aortic artery root dimensions, and valves. ...
Marfan syndrome (MFS), an inherited connective tissue disorder, is caused by a mutation in the FBN1 gene. MFS is characterized by manifestations in the musculoskeletal system (joint laxity, scoliosis), the cardiovascular system (aortic dilation), and the ocular system (ectopic lens). We report a case of a 37-year-old male with a genetically confirmed MFS. His mother and brother were also both confirmed cases of MFS. While the patient exhibited the characteristic physical features of MFS in general appearance, he did not show any cardiac manifestations of the disease. This report highlights a case of the familial occurrence of MFS and emphasizes the importance of recognizing the forme fruste of MFS.
... Because of severe cardiac anomalies and secondary pulmonary manifestations, nMFS is associated with higher morbidity and mortality than classic MFS (Tekin et al. 2007). As nMFS patients suffer from severe mitral and/or tricuspid regurgitation and aortic root dilatation (Stuart and Williams 2007), the clinical course is characterized by rapidly congestive heart failure, and death often occurs within the first year of life (Booms et al. 1999). ...
... Evidence exists to indicate that β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers may reduce the progression of aortic dilatation. However, whether this has a beneficial effect on mortality is unclear (Stuart and Williams 2007;Thakur et al. 2013). Early cardiosurgical intervention may be considered, and cases have been reported in whom corrective cardiac surgery resulted in improved survival (Amado et al. 2014;Kitahara et al. 2016;Carande et al. 2017;Tognato et al. 2019). ...
Neonatal Marfan syndrome (nMFS) is a rare and severe form of Marfan syndrome (MFS) with a poor prognosis, that presents with a highly variable phenotype, particularly regarding skeletal, ocular, and cardiovascular manifestations. Mutations in the fibrillin-1 (FBN1) gene are known as the principal cause of MFS and MFS-related syndromes. Here, we report on a full-term female neonate with postnatal characteristics suggestive of nMFS, including severe cardiovascular disease resulting in cardiorespiratory failure and death by 4 mo of age. We identified a novel large genomic in-frame deletion of FBN1 exons 42-45, c.(5065 + 1_5066 - 1)_(5545 + 1_5546 - 1)del. Large FBN1 in-frame deletions between exons 24 and 53 have been associated with severe MFS. The deletion in our patient differs from the FBN1 region associated with the majority of nMFS cases, exons 24-32.
... Therefore, medical management in these cases includes four main drugs, namely calcium channel blockers, whose action is relaxing the smooth muscles by blocking the calcium channels; angiotensinconverting enzyme inhibitors, which act by inhibiting angiotensin 2 production; angiotensin receptor blockers, which act by inhibiting angiotensin 2 type 1 receptors and thus prevent activation of the reninangiotensin-aldosterone system (RAAS) to promote diuresis; and beta-blockers, which cause myocardial relaxation by blocking beta-1 receptors. These drugs are believed to delay and prevent aortic root dilation [48]. The most commonly used and accepted drug regimen is a combination of beta-blockers supplemented with angiotensin receptor blockers (ARBs) [49]. ...
Marfan syndrome (MFS) is a rare inherited disorder of the connective tissue with an autosomal dominant mode of inheritance which happens as a result of a mutation in the fibrillin-1 (FBN1) gene located on chromosome 15q21.1. This mutation results in the defective formation of microfibrils and increased levels of active transforming growth factor beta (TGF beta), leading to defective connective tissue synthesis. These changes affect various parts of the body but most notably affected are the heart, eyes, and the musculoskeletal system. The standard presenting features of a person suffering from MFS are tall stature with a large arm span, kyphosis, congenital dislocation of the lens (ectopia lentis) and cardiovascular manifestations. The 2010 modified Ghent criteria are used to diagnose MFS on the basis of parameters such as cardiovascular, eye, and musculoskeletal disorders. The cardiovascular manifestations in a patient with MFS are the leading causes of mortality. The most common and dreaded complication is an aortic aneurysm and subsequent dissection. Cardiomyopathy and arrhythmia are also potential killers in such patients. This article aims to look at the various cardiac complications mentioned above and gain an understanding of their pathogenesis, incidence, and outcome. It also includes a brief overview of the rare complication post-Bentall graft infection, and its cause, diagnosis, and management. Various articles by several different authors from around the world were searched for information regarding the pathogenesis, incidence, and outcomes of these patients and are referenced below.
... All possible cases of MFS in the pediatric population should be regularly assessed by echocardiography, optometry, and skeletal survey as the child grows. Children often have an evolving phenotype and commonly need to be followed for several years before a MFS diagnosis can be confirmed (Stuart and Williams 2007). Early referral to a cardiologist and clinical geneticist is key. ...
Marfan syndrome (MFS) is a systemic connective tissue disorder that is inherited in an autosomal dominant pattern with variable penetrance. While clinically this disease manifests in many different ways, the most life-threatening manifestations are related to cardiovascular complications including mitral valve prolapse, aortic insufficiency, dilatation of the aortic root, and aortic dissection. In the past 30 years, research efforts have not only identified the genetic locus responsible but have begun to elucidate the molecular pathogenesis underlying this disorder, allowing for the development of seemingly rational therapeutic strategies for treating affected individuals. In spite of these advancements, the cardiovascular complications still remain as the most life-threatening clinical manifestations. The present chapter will focus on the pathophysiology and clinical treatment of Marfan syndrome, providing an updated overview of the recent advancements in molecular genetics research and clinical trials, with an emphasis on how this information can focus future efforts toward finding betters ways to detect, diagnose, and treat this devastating condition.
