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The Journal of Maternal-fetal &... Jul 2020Early onset Marfan syndrome is the most severe form of Marfan syndrome diagnosed during perinatal period. Early onset Marfan syndrome is associated with high mortality...
Early onset Marfan syndrome is the most severe form of Marfan syndrome diagnosed during perinatal period. Early onset Marfan syndrome is associated with high mortality rates, usually within the first 2 years of life. First, we present a case of prenatally diagnosed early onset Marfan syndrome in a dichorionic diamniotic twin pregnancy, where suspicion was raised at 35 weeks of gestation. Ultrasound and fetal magnetic resonance imaging were used to assess prenatal findings in the affected fetus. She presented right diaphragmatic eventration, elongation of humerus and femur and subluxation of the crystalline lens. She died 3 months after birth. Secondly, we present a PubMed-based review of the published articles on early onset Marfan syndrome, with pre- or postnatal suspicion or diagnosis. We found 39 articles published between 1981 and 2017, arising information on 55 cases. Including ours, early onset Marfan syndrome was prenatally diagnosed in 34.54% of the cases. In these cases, the most frequent prenatal findings were cardiomegaly, dilatation of the great vessels and mitral or tricuspid regurgitation. Mortality rate during the first 15 months after birth was 73.68%. In the postnatally diagnosed cases, the most frequent findings were arachnodactyly, dilatation of the great vessels and mitral or tricuspid regurgitation. Mortality rate was 61.11%. Overall genetic confirmation was performed in 67.27% of the cases. Prenatal diagnosis of early onset Marfan syndrome is challenging but of utmost importance, since management should take place in a tertiary care center, by a multidisciplinary team. Differential diagnosis is essential in order to perform an adequate genetic counseling.
Topics: Adult; Echocardiography; Fatal Outcome; Female; Gestational Age; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Marfan Syndrome; Pregnancy; Pregnancy, Twin; Ultrasonography, Prenatal
PubMed: 30652519
DOI: 10.1080/14767058.2018.1552935 -
European Journal of Vascular and... Oct 2018The aim was to estimate risk of aortic re-operation, and re-operative morbidity and mortality, following replacement of the proximal aorta for aneurysm or dissection. (Meta-Analysis)
Meta-Analysis
OBJECTIVE/BACKGROUND
The aim was to estimate risk of aortic re-operation, and re-operative morbidity and mortality, following replacement of the proximal aorta for aneurysm or dissection.
METHODS
A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Meta-Analysis of Observational Studies in Epidemiology guidelines. A comprehensive literature review was performed to identify all articles reporting aortic re-operation after proximal aortic replacement. The proximal aorta was defined as extending to the origin of the brachiocephalic trunk. The incidence rate for aortic re-operation (IRAR) was calculated, and stratified based on presence/absence of connective tissue disorders, as well as initial surgical indication. Pooled in hospital mortality and post-operative complication rates were estimated.
RESULTS
In total, 7821 patients who underwent proximal aortic replacement from 47 studies were included: 8.3% (n = 649) had Marfan syndrome (MS). During a weighted mean follow up of 4.7 ± 0.3 years, 11.5% (n = 903) underwent aortic re-operation. Mean weighted time between initial surgery and re-operation was 5.2 ± 0.2 years. IRAR was 2.4% per person-year (PPY) (confidence interval [CI] 2.1-2.8%). Patients with MFS had a threefold higher IRAR (6.0% PPY, CI 4.1-8.8%) than did patients without a connective tissue disorders (2.3% PPY, CI 1.9-2.7%; p < .001). IRAR was 2.5% PPY (CI 2.1-3.0%) after operation for dissection and 1.3% PPY (CI 0.9-2.0%) after operation for aneurysm (p = .004 for subgroup differences). IRAR proximal and distal to the left subclavian artery was 1.2% PPY (CI 1.0-1.5%) and 1.3% PPY (CI 1.1-1.6%), respectively. The pooled in hospital mortality and complication rates after re-operation were 14.31% (CI 11.28-17.99%) and 18.08% (CI 10.54-29.25%), respectively. On meta-regression, initial operation for dissection was the only significant predictor of aortic re-operation (beta = .030, p = .001).
CONCLUSION
Aortic re-operation occurs at a mean rate of 2.4% per person-year in the five years after proximal aortic replacement and is strongly associated with initial operation for dissection.
Topics: Aortic Dissection; Aorta; Heart Valve Prosthesis Implantation; Humans; Postoperative Complications; Reoperation; Treatment Outcome
PubMed: 30037741
DOI: 10.1016/j.ejvs.2018.06.038 -
European Journal of Cardio-thoracic... Sep 2018This systemic review of the literature and meta-analysis aimed to evaluate the current state of the evidence for and against reimplantation of the aortic valve (RAV)... (Meta-Analysis)
Meta-Analysis
This systemic review of the literature and meta-analysis aimed to evaluate the current state of the evidence for and against reimplantation of the aortic valve (RAV) versus the composite valve graft (CVG) intervention in patients with Marfan syndrome. Random effects meta-regression was performed across the study arms with logit-transformed proportions of in-hospital deaths as an outcome measure when possible. Results are presented as odds ratios with 95% confidence intervals (CIs) and P-values. Other outcomes are summarized with medians, interquartile ranges (IQR) and ranges and the numbers of patients at risk. Twenty retrospective studies that included a combined 2156 patients with long-term follow-up were identified for analysis after a literature search. The in-hospital mortality rate favoured the RAV procedure with an odds ratio of 0.23 [95% CI 0.09-0.55, P = 0.001]. The survival rate at mid-term for the RAV cohort was 96.7% (CI 94.2-98.5) vs. 86.4% (CI 82.8-89.6) for the CVG group and 93.1% (CI 66.4-100) for the RAV group vs. 82.6% (CI 74.9-89.2) for the CVG group for the long term. Freedom from valve-related reintervention (median percentages) for the long term was 97.6% (CI 90.3-100%) for the RAV procedure and 88.6% (CI 79.1-95.5) for a CVG. This systematic review of the literature stresses the advantages of the RAV procedure in patients with Marfan syndrome in regard to long- and short-term results as the treatment of choice in aortic root surgery. The RAV procedure reduces in-hospital as well as long-term deaths and protects against aortic valve reintervention.
Topics: Adolescent; Adult; Aorta; Aortic Valve; Blood Vessel Prosthesis Implantation; Female; Heart Valve Prosthesis Implantation; Humans; Male; Marfan Syndrome; Replantation; Retrospective Studies; Young Adult
PubMed: 29893811
DOI: 10.1093/ejcts/ezy158 -
American Journal of Medical Genetics.... Aug 201822q11.2 deletion syndrome (22q11.2DS) is associated with high rates of anxiety disorders, psychotic disorders, and other psychiatric conditions. In the general...
22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of anxiety disorders, psychotic disorders, and other psychiatric conditions. In the general population, psychiatric disorders are treated with proven pharmacological and non-pharmacological therapies, such as cognitive behavioral therapy (CBT). To begin to assess the feasibility and efficacy of non-pharmacological therapies in 22q11.2DS, we performed a systematic search to identify literature on non-pharmacological interventions for psychiatric disorders in individuals with 22q11.2DS. Of 1,240 individual publications up to mid-2016 initially identified, 11 met inclusion criteria. There were five literature reviews, five publications reporting original research (two originating from a single study), and one publication not fitting either category that suggested adaptations to an intervention without providing scientific evidence. None of the original research involved direct study of the evidence-based non-pharmacological therapies available for psychiatric disorders. Rather, these four studies involved computer-based or group interventions aimed at improving neuropsychological deficits that may be associated with psychiatric disorders. Although the sample sizes were relatively small (maximum 28 participants in the intervention group), these reports documented the promising feasibility of these interventions, and improvements in domains of neuropsychological functioning, including working memory, attention, and social cognition. The results of this review underline the need for research into the feasibility and efficacy of non-pharmacological treatments of psychiatric disorders in individuals with 22q11.2DS to inform clinical care, using larger samples, and optimally, standard randomized, placebo-controlled, clinical trials methodology.
Topics: Adult; Arachnodactyly; Cognitive Behavioral Therapy; Craniosynostoses; DiGeorge Syndrome; Female; Humans; Male; Marfan Syndrome; Psychotic Disorders
PubMed: 29363845
DOI: 10.1002/ajmg.a.38612 -
Annals of Cardiothoracic Surgery Nov 2017A major, life-limiting feature of Marfan syndrome (MFS) is the presence of aneurysmal disease. Cardiovascular intervention has dramatically improved the life expectancy... (Review)
Review
BACKGROUND
A major, life-limiting feature of Marfan syndrome (MFS) is the presence of aneurysmal disease. Cardiovascular intervention has dramatically improved the life expectancy of Marfan patients. Traditionally, the management of aortic root disease has been undertaken with composite-valve graft replacing the aortic valve and proximal aorta; more recently, valve sparing procedures have been developed to avoid the need for anticoagulation. This meta-analysis assesses the important surgical outcomes of the two surgical techniques.
METHODS
A systematic review and meta-analysis of 23 studies reporting the outcomes of aortic root surgery in Marfan patients with data extracted for outcomes of early and late mortality, thromboembolic events, late bleeding complications and surgical reintervention rates.
RESULTS
The outcomes of 2,976 Marfan patients undergoing aortic root surgery were analysed, 1,624 patients were treated with composite valve graft (CVG) and 1,352 patients were treated with valve sparing root replacement (VSRR). When compared against CVG, VSRR was associated with reduced risk of thromboembolism (OR =0.32; 95% CI, 0.16-0.62, P=0.0008), late hemorrhagic complications (OR =0.18; 95% CI, 0.07-0.45; P=0.0003) and endocarditis (OR =0.27; 95% CI, 0.10-0.68; P=0.006). Importantly there was no significant difference in reintervention rates between VSRR and CVG (OR =0.89; 95% CI, 0.35-2.24; P=0.80).
CONCLUSIONS
There is an increasing body of evidence that VSRR can be reliably performed in Marfan patients, resulting in a durable repair with no increased risk of re-operation compared to CVG, thus avoiding the need for systemic anticoagulation in selected patients.
PubMed: 29270369
DOI: 10.21037/acs.2017.11.06 -
Open Heart 2017Our understanding of inherited heart disease is predominantly based on retrospective specialised clinic cohorts, which have inherent selection bias. Population-based...
OBJECTIVE
Our understanding of inherited heart disease is predominantly based on retrospective specialised clinic cohorts, which have inherent selection bias. Population-based routinely collected data can provide insight into unbiased, large-scale patterns of treatment and care but may be limited by the granularity of clinical information available. We sought to synthesise the global literature to determine whether we can identify patients with inherited heart diseases using routinely collected health data.
METHODS
Medline, Embase, CINAHL, PreMEDLINE and Google Scholar citation databases were searched for relevant articles published between 1 January 2000 and 31 October 2016.
RESULTS
A total of 5641 titles/abstracts were screened and 46 full-text articles were retrieved. Twelve peer-reviewed, English-language manuscripts met our inclusion criteria. Studies predominantly focused on Marfan syndrome (41%) or hypertrophic cardiomyopathy (29%). All studies used International Classification of Disease diagnosis codes to define inherited heart disease populations; three studies also used procedure codes. Nine of the 17 definitions for inherited heart disease were repeated across studies.
CONCLUSIONS
Inherited heart disease populations can be identified using routinely collected health data, though challenges relate to existing diagnosis codes. This is an underutilised resource with the potential to inform patterns of care, patient outcomes and overall disease burden.
PubMed: 29209507
DOI: 10.1136/openhrt-2017-000686 -
The Cochrane Database of Systematic... Nov 2017Marfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the... (Review)
Review
BACKGROUND
Marfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural and pulmonary systems. Aortic root dilatation is the most frequent cardiovascular manifestation and its complications, including aortic regurgitation, dissection and rupture are the main cause of morbidity and mortality.
OBJECTIVES
To assess the long-term efficacy and safety of beta-blocker therapy as compared to placebo, no treatment or surveillance only in people with Marfan syndrome.
SEARCH METHODS
We searched the following databases on 28 June 2017; CENTRAL, MEDLINE, Embase, Science Citation Index Expanded and the Conference Proceeding Citation Index - Science in the Web of Science Core Collection. We also searched the Online Metabolic and Molecular Bases of Inherited Disease (OMMBID), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 June 2017. We did not impose any restriction on language of publication.
SELECTION CRITERIA
All randomised controlled trials (RCTs) of at least one year in duration assessing the effects of beta-blocker monotherapy compared with placebo, no treatment or surveillance only, in people of all ages with a confirmed diagnosis of Marfan syndrome were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts for inclusion, extracted data and assessed trial quality. Trial authors were contacted to obtain missing data. Dichotomous outcomes will be reported as relative risk and continuous outcomes as mean differences with 95% confidence intervals. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
One open-label, randomised, single-centre trial including 70 participants with Marfan syndrome (aged 12 to 50 years old) met the inclusion criteria. Participants were randomly assigned to propranolol (N = 32) or no treatment (N = 38) for an average duration of 9.3 years in the control group and 10.7 years in the treatment group. The initial dose of propranolol was 10 mg four times daily and the optimal dose was reached when the heart rate remained below 100 beats per minute during exercise or the systolic time interval increased by 30%. The mean (± standard error (SE)) optimal dose of propranolol was 212 ± 68 mg given in four divided doses daily.Beta-blocker therapy did not reduce the incidence of all-cause mortality (RR 0.24, 95% CI 0.01 to 4.75; participants = 70; low-quality evidence). Mortality attributed to Marfan syndrome was not reported. Non-fatal serious adverse events were also not reported. However, study authors report on pre-defined, non-fatal clinical endpoints, which include aortic dissection, aortic regurgitation, cardiovascular surgery and congestive heart failure. Their analysis showed no difference between the treatment and control groups in these outcomes (RR 0.79, 95% CI 0.37 to 1.69; participants = 70; low-quality evidence).Beta-blocker therapy did not reduce the incidence of aortic dissection (RR 0.59, 95% CI 0.12 to 3.03), aortic regurgitation (RR 1.19, 95% CI 0.18 to 7.96), congestive heart failure (RR 1.19, 95% CI 0.18 to 7.96) or cardiovascular surgery, (RR 0.59, 95% CI 0.12 to 3.03); participants = 70; low-quality evidence.The study reports a reduced rate of aortic dilatation measured by M-mode echocardiography in the treatment group (aortic ratio mean slope: 0.084 (control) vs 0.023 (treatment), P < 0.001). The change in systolic and diastolic blood pressure, total adverse events and withdrawal due to adverse events were not reported in the treatment or control group at study end point.We judged this study to be at high risk of selection (allocation concealment) bias, performance bias, detection bias, attrition bias and selective reporting bias. The overall quality of evidence was low. We do not know whether a statistically significant reduced rate of aortic dilatation translates into clinical benefit in terms of aortic dissection or mortality.
AUTHORS' CONCLUSIONS
Based on only one, low-quality RCT comparing long-term propranolol to no treatment in people with Marfan syndrome, we could draw no definitive conclusions for clinical practice. High-quality, randomised trials are needed to evaluate the long-term efficacy of beta-blocker treatment in people with Marfan syndrome. Future trials should report on all clinically relevant end points and adverse events to evaluate benefit versus harm of therapy.
Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aortic Dissection; Humans; Marfan Syndrome; Middle Aged; Propranolol; Young Adult
PubMed: 29110304
DOI: 10.1002/14651858.CD011103.pub2 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2016Rare diseases (RD) are those that present a lower prevalence than 5 cases per 10.000 population. The main objective of this review was to study the effect on oral health... (Review)
Review
BACKGROUND
Rare diseases (RD) are those that present a lower prevalence than 5 cases per 10.000 population. The main objective of this review was to study the effect on oral health in rare diseases, while the secondary objective of the study is theme upgrade.
MATERIAL AND METHODS
Comparative observational case-control studies were analysed and a systematic review was conducted in PubMed. Each rare disease listed on the statistical data record of the Health Portal of the Ministry of Equality, Health and Social Policies Board of Andalusia was associated with "oral health". The variables studied included dental, oral mucosa and occlusion alterations, oral pathologies (caries, periodontal disease) and other alterations (mouth breathing, parafunctional habits, etc). A bias analysis of the variable caries was conducted.
RESULTS
Six RD were selected through our inclusion and exclusion criteria (hypogammaglobulinemia, Rett syndrome, Marfan syndrome, Prader-Willi syndrome, cystic fibrosis and Cri du chat syndrome) in a total of 8 publications, of which four trials were classified as high risk of bias and one of them as medium risk. There were not trials with low risk of bias.
CONCLUSIONS
The main statistically significant differences found by Syndrome compared to a control group were in Hypogammaglobulinemia with a greater tendency to enamel hypoplasia and dry mouth. The Rett syndrome had, as well, a greater tendency to an anterior open bite, ogival palate, bruxism, mouth breathing and tongue thrusting. Prader-Willi syndrome had a tendency of dental erosion, and Cri du chat syndrome showed a higher association to Tannerella forsythia.
Topics: Bruxism; Cri-du-Chat Syndrome; Dental Caries; Humans; Oral Health; Rare Diseases
PubMed: 27475682
DOI: 10.4317/medoral.20972 -
International Journal of Cardiology Aug 2016To assess the effect of losartan therapy on progressive aortic dilatation and on clinical outcome in patients with Marfan's syndrome (MFS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the effect of losartan therapy on progressive aortic dilatation and on clinical outcome in patients with Marfan's syndrome (MFS).
METHODS
The meta-analysis was instituted, which included studies identified by a systematic review of MEDLINE of peer-reviewed publications. Echocardiogram or MRI measurements of the aortic root dimension and outcome measures of death, cardiovascular surgery and aortic dissection or rupture were compared between patients who were treated and untreated with losartan therapy.
RESULTS
Six randomized trials with 1398 subjects met all the inclusion criteria and were included in the meta-analysis. Compared with non-losartan treatment, losartan therapy significantly decreased the rate of aortic dilatation (SMD=-0.13 with 95% CI -0.25 to 0.00, p=0.04). The clinical outcome beneficial was not observed in the losartan treatment group when compared with no losartan treatment group (odds ratio=1.04 with 95% CI of 0.57-1.87).
CONCLUSION
Given the current results of the meta-analysis and together with the lack of associated side effects, it would be reasonable to use losartan in MFS patients with aortic root dilatation. However, no clinical outcome benefits were observed in the losartan treatment group when compared with no losartan treatment group.
Topics: Aortic Diseases; Dilatation, Pathologic; Echocardiography; Female; Humans; Losartan; Magnetic Resonance Imaging; Male; Marfan Syndrome; Prospective Studies; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 27187761
DOI: 10.1016/j.ijcard.2016.04.186 -
European Journal of Vascular and... May 2016The growth rates of thoracic aortic aneurysms (TAAs) and factors influencing their expansion are poorly understood. This study aimed to review systematically published... (Review)
Review
OBJECTIVE/BACKGROUND
The growth rates of thoracic aortic aneurysms (TAAs) and factors influencing their expansion are poorly understood. This study aimed to review systematically published literature describing TAA expansion and examine factors that may be associated with this.
METHODS
A comprehensive search of MEDLINE and Embase databases was performed until 30 April 2015. Studies describing rates of TAA growth were identified and systematically reviewed. Outcomes of interest were TAA growth rates and associated factors. Study quality was assessed using Scottish Intercollegiate Guidelines Network quality checklists for cohort studies.
RESULTS
Eleven publications, involving 1383 patients, met the eligibility criteria and were included in the review. Included studies were generally low in quality. Aneurysm measurement and growth-rate estimation techniques were inconsistently reported. Mean growth rates for all TAAs ranged from 0.2 to 4.2 mm/year. Mean growth rates for ascending and aortic arch aneurysms ranged from 0.2 to 2.8 mm/year, while those for descending and thoracoabdominal aneurysms ranged from 1.9 to 3.4 mm/year in studies reporting according to anatomical location. Large aneurysm size, distal aneurysm locations, presence of Marfan's syndrome, and bicuspid aortic valve were consistently associated with accelerated TAA growth. Presence of chronic dissection and chronic obstructive pulmonary disorder were also implicated as risk factors for faster TAA growth. Associations between medical comorbidity and aneurysm expansion were conflicting. Previous aortic surgery and anticoagulants were reported to have a protective effect on aneurysm growth in two studies.
CONCLUSION
There is a shortfall in the understanding of TAA expansion rates. Existing studies are heterogeneous in methodology and reported outcomes. Identified unifying themes suggest that TAAs grow at a slow rate with large presenting diameter, distal aneurysm, and history of bicuspid aortic valve or Marfan's syndrome serving as main risk factors for accelerated aneurysm growth. High-quality studies with a standardised approach to TAA growth assessment are required.
Topics: Aortic Aneurysm, Thoracic; Disease Progression; Humans; Risk Factors
PubMed: 26947541
DOI: 10.1016/j.ejvs.2016.01.017