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Birth Defects Research Dec 2020Mutations in the transforming growth factor β-binding protein-like domain 5 (TB5) region of FBN1 can lead to autosomal acromelic dysplasia and Marfan syndrome, which...
Mutations in the transforming growth factor β-binding protein-like domain 5 (TB5) region of FBN1 can lead to autosomal acromelic dysplasia and Marfan syndrome, which are two diseases with apparently opposite phenotypes. We identified six patients with acromelic dysplasia carrying either the previously reported mutations c.5284G > A (p.Gly1762Ser) and c.5096A > G (p.Tyr1699Cys) or the novel mutation c.5260G > A (p.Gly1754Ser). A systematic review of patients with mutations in the FBN1-TB5 region showed that acromelic dysplasia is caused only by in-frame amino acid substitutions. In contrast, truncating mutations in the FBN1-TB5 have been reported only in Marfan syndrome. Acromelic dysplasia subtypes that share symptoms with Marfan syndrome are associated with FBN1-TB5 disulfide disruptions, which are also commonly found in Marfan syndrome. These results suggest that the type and location of mutations in the FBN1-TB5 region determine the clinical spectrum of fibrillinopathy.
Topics: Arthrogryposis; Fibrillin-1; Humans; Marfan Syndrome; Mutation; Phenotype
PubMed: 33030311
DOI: 10.1002/bdr2.1814 -
Diagnostics (Basel, Switzerland) Sep 2020Marfan syndrome (MFS) is a heritable systemic connective tissue disease with important cardiovascular involvement, including aortic root dilatation and mitral valve... (Review)
Review
Marfan syndrome (MFS) is a heritable systemic connective tissue disease with important cardiovascular involvement, including aortic root dilatation and mitral valve prolapse. Life expectancy in patients with MFS is mainly determined by cardiovascular complications, among which aortic dissection or rupture are most dreaded. In recent years, heart failure and ventricular arrhythmia have drawn attention as extra-aortic cardiovascular manifestations and as additional reported causes of death. Imaging studies have provided data supporting a primary myocardial impairment in the absence of valvular disease or cardiovascular surgery, while studies using ambulatory ECG have demonstrated an increased susceptibility to ventricular arrhythmia. In this paper, current literature was reviewed in order to provide insights in characteristics, pathophysiology and evolution of myocardial function, heart failure and ventricular arrhythmia in MFS.
PubMed: 32992882
DOI: 10.3390/diagnostics10100751 -
Orphanet Journal of Rare Diseases Aug 2019Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50-60% of them. The cause of the phenotypic variability is unknown. Patients usually harbor one of three common deletions sizes: 3, 2 and 1.5 Mb, between low copy repeats (LCR) designated A-D, A-C and A-B, respectively. This study aimed to analyze the association between these 3 deletion sizes and the presence of congenital cardiac and/or palatal malformations in individuals with this condition. A systematic review and meta-analysis were conducted, merging relevant published studies with data from Chilean patients to increase statistical power.
RESULTS
Eight articles out of 432 were included; the data from these studies was merged with our own, achieving a total of 1514 and 487 patients to evaluate cardiac and palate malformations, respectively. None of the compared deleted chromosomal segments were statistically associated with cardiac defects (OR: 0.654 [0.408-1.046]; OR : 1.291 [0.860-1.939]) or palate anomalies (OR: 1.731 [0.708-4.234]; OR : 0.628 [0.286-1.382]).
CONCLUSIONS
The lack of association between deletion size and CHD or PA found in this meta-analysis suggests that deletion size does not explain the incomplete penetrance of these 2 major manifestations, and that the critical region for the development of heart and palatal abnormalities is within LCR A-B, the smallest region of overlap among the three deletion sizes.
Topics: Arachnodactyly; Chromosome Deletion; Craniosynostoses; Humans; Marfan Syndrome; Phenotype
PubMed: 31399107
DOI: 10.1186/s13023-019-1170-x -
European Journal of Preventive... Sep 2020
Meta-Analysis
Topics: Angiotensin II Type 1 Receptor Blockers; Aortic Aneurysm; Humans; Losartan; Marfan Syndrome
PubMed: 31260329
DOI: 10.1177/2047487319861231 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2019The purpose was to identify and assess the existing scientific evidence from epidemiologic, non-experimental, observational studies of associations between Marfan's... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose was to identify and assess the existing scientific evidence from epidemiologic, non-experimental, observational studies of associations between Marfan's syndrome and oral diseases.
MATERIAL AND METHODS
Electronic literature searches in MEDLINE (OVID), The Cochrane Library, Scopus and the Web of Science were conducted to identify all relevant articles. Eligibility was based on inclusion criteria, and quality assessments were conducted. The outcome variables were probing depth, gingival margin, clinical attachment level, bleeding on probing, gingival status, periodontal status, tooth mobility, furcation involvement and decayed, missing and filled teeth index. After extracting data, meta-analyses were carried out.
RESULTS
Out of 527 potentially eligible papers, 3 cross-sectional studies were included. No statistically significant differences were found in the number of sites with bleeding on probing (OR: 1.26; 95% CI: 0.47 to 3.42; P = 0.65; I2: 0%), probing depth (MD: -0.14 mm; 95% CI: -0.24 to 0.53; P = 0.46; I2: 93%), periodontal status (WMD: 0.68 points; 95% CI: -0.48 to 1.83; P = 0.25; I2: 98%) nor number of decayed, missing and filled teeth index score (MD: 1.08 points.; 95% CI: -1.27 to 3.42; P = 0.37; I2: 0%).
CONCLUSIONS
Patients diagnosed with Marfan's syndrome do not seem to have worsened oral health status. Due to the high number of patients with Marfan's syndrome that have prosthetic heart valves, an adequate dental monitoring as well as a strict maintenance therapy program should be implemented.
Topics: Cross-Sectional Studies; Humans; Marfan Syndrome; Oral Health
PubMed: 31232392
DOI: 10.4317/medoral.23037 -
Journal of the Formosan Medical... Jan 2020Variable effects of beta-blockers (BB) and/or angiotensin receptor blockers (ARB) were reported to retard aortic root growth in Marfan syndrome (MFS). This study aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Variable effects of beta-blockers (BB) and/or angiotensin receptor blockers (ARB) were reported to retard aortic root growth in Marfan syndrome (MFS). This study aimed to compare the effects of BB therapy and ARB-related therapies on cardiovascular protection in MFS.
METHODS
Studies of randomized control trials comparing the efficacy of only-BB and ARB-related (only-ARB or ARB-plus-BB) therapies for MFS published before July 31, 2018 in PubMed, Embase, and the Cochrane Library were selected. The outcomes included changes in aortic growth and cardiovascular events.
RESULTS
Eight trials involving 1381 patients were included. Patients received only-BB and ARB-related therapies did not differ significantly in changes in aortic growth (aortic root diameter: standardized mean difference [SMD] = 0.04, 95% confidence interval [CI]: -0.11-0.19, p = 0.63) or cardiovascular events (aortic dissection: Peto odds ratio [OR] = 1.67, 95% CI: 0.42-6.72, p = 0.47; aortic surgery: risk ratio = 0.97, 95% CI: 0.66-1.41, p = 0.86; death: Peto OR = 2.78, 95% CI: 0.39-19.82, p = 0.31). Subgroup analysis revealed that ARB-plus-BB therapy exhibited nonsignificantly better outcomes than only-BB therapy (aortic root diameter: SMD = 0.11, 95% CI: -0.22-0.45, p = 0.52; ascending aorta diameter: SMD = 0.10, 95% CI: -0.07-0.27, p = 0.26; aortic surgery: Peto OR = 1.10, 95% CI: 0.75-1.61, p = 0.62).
CONCLUSION
For cardiovascular protection in MFS, only-ARB therapy is not inferior to only-BB therapy. Moreover, the outcomes of ARB-plus-BB therapy seemed to be favourable to those of only-BB therapy.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Aortic Diseases; Cardiotonic Agents; Dilatation, Pathologic; Drug Therapy, Combination; Humans; Losartan; Marfan Syndrome; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31003918
DOI: 10.1016/j.jfma.2019.03.018 -
Management and Outcomes of Aortic Dissection in Pregnancy with Marfan Syndrome: A Systematic Review.Current Vascular Pharmacology 2020In Marfan Syndrome (MFS), aortic dilatation is one of the main cardiovascular manifestations which deteriorate due to the physiological changes during pregnancy. We...
BACKGROUND
In Marfan Syndrome (MFS), aortic dilatation is one of the main cardiovascular manifestations which deteriorate due to the physiological changes during pregnancy. We aimed to assess the up-to-date management and outcomes of aortic root dilation and dissection (AoD) in pregnancy with MFS.
PATIENTS AND METHODS
A systematic review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Original studies published between January 1, 2001 and December 31, 2018 and which described the management and/or outcomes of AoD during or after pregnancy in women with MFS were included. Literature searches were conducted. The PubMed search was performed using terms "Marfan Syndrome" [Mesh] and "Pregnancy" [Mesh] whereas the Google Scholar search was for "Marfan" and "Pregnancy", all words anywhere in the article.
RESULTS
The literature search yielded 177 articles on PubMed and 13,900 articles on Google Scholar. Assessment of full-text articles for eligibility after removal of duplicates from both databases yielded 12 eligible studies to be included in the final review.
CONCLUSION
Women with MFS are at high risk of aortic dissection during pregnancy and women with aortic root 41-45 mm should consider avoiding pregnancy. Guideline-specific management of aortic aneurysms in pregnancy will reduce the risk of dissection. Diagnosis and Management of MFS need a multidisciplinary approach and team that should start working early in pregnancy. Further studies are needed to optimize medical and surgical approaches in addition to preconception counselling in highrisk subjects.
Topics: Aortic Dissection; Aortic Aneurysm; Blood Vessel Prosthesis Implantation; Female; Heart Valve Prosthesis Implantation; Humans; Marfan Syndrome; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 30963974
DOI: 10.2174/1570161117666190408164612 -
Expert Review of Cardiovascular Therapy Apr 2019Current guidelines recommend patients with thoracic aortic disease (TAD) including inherited aortopathies to avoid heavy exercise. However, evidence supporting the...
Current guidelines recommend patients with thoracic aortic disease (TAD) including inherited aortopathies to avoid heavy exercise. However, evidence supporting the negative advice on exercise is scarce. We aimed to provide an up-to-date systematic review of the available evidence on risks and benefits of exercise and sports participation in TAD patients. Areas covered: A systematic search was performed in Medline, Embase and Web of Science: thoracic aortic aneurysm or thoracic aortic dissection or inheritable aortopathies including Marfan Syndrome (MFS), Loeys-Dietz syndrome, Turner Syndrome, Ehlers-Danlos syndrome, bicuspid aortic valve (BAV) and sports, exercise or athletes. The resulting 1,652 manuscripts were reviewed by two independent observers. Eventually, 26 studies and 12 case-reports were included, reporting on thoracic aortic dimensions in athletes, exercise related acute aortic dissections, and exercise in BAV and MFS patients. Expert opinion: Blood pressure elevation during exercise may be associated with an increased risk of acute aortic dissection; however, no controlled trials have longitudinally evaluated the effect of exercise on survival or the risk of aortic dissection in TAD patients. Mouse-model studies suggest beneficial effects of exercise in the setting of a dilated aorta in MFS. There is a clear need for prospective research in this field.
Topics: Animals; Aorta, Thoracic; Aortic Diseases; Disease Models, Animal; Exercise; Humans; Mice; Risk Assessment; Sports
PubMed: 30887852
DOI: 10.1080/14779072.2019.1585807 -
Clinical Genetics Jun 2019The purpose of this study was to explore the literature on quality of life (QoL) in patients with hereditary thoracic aortic aneurysm and dissection (HTAAD); including...
The purpose of this study was to explore the literature on quality of life (QoL) in patients with hereditary thoracic aortic aneurysm and dissection (HTAAD); including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS) and other HTAAD diagnoses, critically appraising and synthesizing the relevant literature. A systematic review was performed by searching the published literature using available medical, physical, psychological, social databases and other sources. Studies addressing QoL in persons with an HTAAD diagnosis, published in peer-reviewed journals were assessed. Of 227 search results, 20 articles satisfied the eligibility criteria. No studies of QoL in LDS, vEDS, or other HTAAD were found, only on MFS. Most studies had been published in the last 3 years. All were cross-sectional quantitative studies besides one pilot intervention study. Most studies were of small sample size, had low response rate or participants without verified diagnosis. Despite these limitations, most studies indicate that having an HTAAD diagnosis as MFS may negatively impact QoL, but few studies found any associations between the biomedical symptoms and decreased QoL. More research is needed on QoL in samples with verified HTAAD diagnosis to develop evidence-based knowledge and appropriate guidelines for these diagnoses.
Topics: Adult; Aortic Dissection; Aortic Aneurysm, Thoracic; Child; Cross-Sectional Studies; Delivery of Health Care; Ehlers-Danlos Syndrome; Humans; Loeys-Dietz Syndrome; Marfan Syndrome; Quality of Life; Sample Size
PubMed: 30788842
DOI: 10.1111/cge.13522 -
Journal of Clinical Sleep Medicine :... Feb 2019Because of associated abnormalities affecting connective tissue in various organs including airways, hypermobility syndrome has been associated with high risk for the... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Because of associated abnormalities affecting connective tissue in various organs including airways, hypermobility syndrome has been associated with high risk for the development sleep apnea. Ehlers-Danlos syndrome (EDS) and Marfan syndrome (MFS) represent the most common hypermobility syndromes; therefore, the purpose of this review was to examine the prevalence of obstructive sleep apnea (OSA) in these populations.
METHODS
All publications and poster presentations written in English found through August 2018 that describe the prevalence of sleep apnea among people with EDS or MFS were included.
RESULTS
A total of 13 studies were identified, 7 for EDS and 6 for MFS. A combined random prevalence rate of OSA across both populations was 48.9% (95% confidence interval 38.3-59.6), with a slightly higher rate of 59.7% (39.7-77.0) for MFS versus 39.4% (28.8-51.1) for EDS. However, a high degree of heterogeneity across studies was found in both groups (EDS group: Q = 28.6 and = 79.0; MFS group: Q = 37.1 and = 86.5). When directly compared to the general population, patients with EDS/MFS were on average six times more likely (odds ratio 6.28 [95% confidence interval 3.31-11.93], < 0.001, Z = 5.61) to have a diagnosis of OSA.
CONCLUSIONS
OSA is a previously underestimated EDS/MFS-related complication. The high prevalence of OSA might be the result of bony and soft-tissue abnormalities associated with these hypermobility syndromes. Untreated OSA is thought to worsen cardiovascular complications especially among those with MFS. Further research is needed to better delineate whether the prevalence of OSA is moderated by factors such as sex, body mass index, bony structure, and disorder subtype.
Topics: Comorbidity; Cross-Sectional Studies; Ehlers-Danlos Syndrome; Humans; Joint Instability; Marfan Syndrome; Odds Ratio; Sleep Apnea, Obstructive
PubMed: 30736885
DOI: 10.5664/jcsm.7636