-
Acta Ophthalmologica Jun 2021To investigate the corneoscleral shape in Marfan syndrome (MFS) patients.
PURPOSE
To investigate the corneoscleral shape in Marfan syndrome (MFS) patients.
METHODS
Thirty eyes of 15 participants with molecularly proven MFS were included in this prospective, cross-sectional study. Optical biometry, Scheimpflug imaging, and corneoscleral topography (Eye Surface Profiler) were performed in all patients. Topographic data were compared to data from controls (25 emmetropes and 17 myopes). The raw three-dimensional anterior height data from MFS eyes and control eyes were exported for further analysis. Custom-made software was used to demarcate the limbal radius and to calculate the sagittal height in different concentric annuli centred at the corneal apex, placed in a pupil plane, for the central cornea (0-4 mm radius), peripheral cornea (4-6 mm radius) and sclera (6-8 mm radius) and the corneoscleral asymmetry.
RESULTS
Marfan syndrome (MFS) eyes had significantly lower values of mean sagittal height compared to non-MFS eyes in all three annuli (central cornea, corneal periphery and sclera (independent t-test, p < 0.01 except for the inferior area of the scleral radius: p > 0.05). The sclera was significantly more asymmetric in MFS eyes compared to myopes (independent t-test, p < 0.01 for both eyes), but similar to emmetropes (independent t-test, p = 0.17 and p = 0.93 for right and left eyes, respectively). In MFS eyes, scleral asymmetry was not found to be correlated with axial length (Pearson correlation coefficient, r < 0.30, p > 0.05).
CONCLUSION
The peripheral cornea and sclera of Marfan syndrome patients have a significantly different shape compared to healthy controls.
Topics: Adult; Cornea; Corneal Topography; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Male; Marfan Syndrome; Middle Aged; Prospective Studies; Refraction, Ocular; Sclera; Young Adult
PubMed: 32996688
DOI: 10.1111/aos.14636 -
Current Cardiology Reviews May 2014Thoracic aortic aneurysms can be triggered by genetic disorders such as Marfan syndrome (MFS) and related aortic diseases as well as by inflammatory disorders such as... (Review)
Review
Thoracic aortic aneurysms can be triggered by genetic disorders such as Marfan syndrome (MFS) and related aortic diseases as well as by inflammatory disorders such as giant cell arteritis or atherosclerosis. In all these conditions, cardiovascular risk factors, such as systemic arterial hypertension, may contribute to faster rate of aneurysm progression. Optimal medical management to prevent progressive aortic dilatation and aortic dissection is unknown. β-blockers have been the mainstay of medical treatment for many years despite limited evidence of beneficial effects. Recently, losartan, an angiotensin II type I receptor antagonist (ARB), has shown promising results in a mouse model of MFS and subsequently in humans with MFS and hence is increasingly used. Several ongoing trials comparing losartan to β-blockers and/or placebo will better define the role of ARBs in the near future. In addition, other medications, such as statins and tetracyclines have demonstrated potential benefit in experimental aortic aneurysm studies. Given the advances in our understanding of molecular mechanisms triggering aortic dilatation and dissection, individualized management tailored to the underlying genetic defect may be on the horizon of individualized medicine. We anticipate that ongoing research will address the question whether such genotype/pathogenesis-driven treatments can replace current phenotype/syndrome-driven strategies and whether other forms of aortopathies should be treated similarly. In this work, we review currently used and promising medical treatment options for patients with heritable aortic aneurysmal disorders.
Topics: Animals; Aortic Aneurysm; Clinical Trials as Topic; Disease Progression; Genotype; Humans; Marfan Syndrome; Risk Factors
PubMed: 24527681
DOI: 10.2174/1573403x1002140506124902 -
Journal of Medical Genetics Jan 2000Mutations in the gene for fibrillin-1 (FBN1) have been shown to cause Marfan syndrome, an autosomal dominant disorder of connective tissue characterised by pleiotropic... (Review)
Review
Mutations in the gene for fibrillin-1 (FBN1) have been shown to cause Marfan syndrome, an autosomal dominant disorder of connective tissue characterised by pleiotropic manifestations involving primarily the ocular, skeletal, and cardiovascular systems. Fibrillin-1 is a major component of the 10-12 nm microfibrils, which are thought to play a role in tropoelastin deposition and elastic fibre formation in addition to possessing an anchoring function in some tissues. Fibrillin-1 mutations have also been found in patients who do not fulfil clinical criteria for the diagnosis of Marfan syndrome, but have related disorders of connective tissue, such as isolated ectopia lentis, familial aortic aneurysm, and Marfan-like skeletal abnormalities, so that Marfan syndrome may be regarded as one of a range of type 1 fibrillinopathies. There appear to be no particular hot spots since mutations are found throughout the entire fibrillin-1 gene. However, a clustering of mutations associated with the most severe form of Marfan syndrome, neonatal Marfan syndrome, has been noted in a region encompassing exons 24 to 32. The gene for fibrillin-2 (FBN2) is highly homologous to FBN1, and mutations in FBN2 have been shown to cause a phenotypically related disorder termed congenital contractural arachnodactyly. Since mutations in the fibrillin genes are likely to affect the global function of the microfibrils, the term microfibrillopathy may be the most appropriate to designate the spectrum of disease associated with dysfunction of these molecules. The understanding of the global and the molecular functions of the fibrillin containing microfibrils is still incomplete and, correspondingly, no comprehensive theory of the pathogenesis of Marfan syndrome has emerged to date. Many, but not all, fibrillin-1 gene mutations are expected to exert a dominant negative effect, whereby mutant fibrillin monomers impair the global function of the microfibrils. In this paper we review the molecular physiology and pathophysiology of Marfan syndrome and related microfibrillopathies.
Topics: Abnormalities, Multiple; Chromosome Mapping; Chromosomes, Human, Pair 3; Fibrillin-1; Fibrillin-2; Fibrillins; Humans; Marfan Syndrome; Microfilament Proteins; Mutation
PubMed: 10633129
DOI: 10.1136/jmg.37.1.9 -
European Journal of Cardio-thoracic... Oct 2022The aim of this study was to explore sex and gender differences regarding aortic events in Marfan patients.
OBJECTIVES
The aim of this study was to explore sex and gender differences regarding aortic events in Marfan patients.
METHODS
We analysed all data from our connective tissue disorder database. Only patients with Marfan syndrome were included. For analysis, patients were divided by sex. Female patients were further divided into 2 subgroups: with versus without children. Aortic events were defined as Stanford type A aortic dissection (TAAD) or type B aortic dissection (TBAD) or any aortic intervention.
RESULTS
A population of 183 Marfan patients was analysed for the purpose of this study. One hundred four (57%) were male and 79 (43%) were female patients. Thirty-seven (47%) of the 79 female patients had at least 1 child. Male patients had a significantly higher probability of experiencing an aortic event (P = 0.015) compared to female patients. However, there was no increased probability for recurrent events in male patients compared to female patients (P = 0.063). Follow-up revealed no sex and gender differences in the occurrence of Stanford TAAD or TBAD between male and female patients (P = 0.324/P = 0.534). While 11% of women with children suffered from peripartum aortic events, 24% experienced Stanford TAAD unrelated to pregnancy.
CONCLUSIONS
Male patients have a higher risk of aortic events than female patients. The majority of women were not aware of their Marfan syndrome diagnosis before conceiving. One out of 10 women suffered from peripartum Stanford TAAD or TBAD. Twice as many female patients with children suffered from aortic dissection unrelated to childbirth. There were no sex and gender differences affecting mortality in Marfan patients.
Topics: Child; Humans; Female; Male; Marfan Syndrome; Aortic Dissection; Aorta
PubMed: 35543473
DOI: 10.1093/ejcts/ezac305 -
Journal of the American College of... Jul 2012
Topics: Aorta; Female; Humans; Marfan Syndrome; Pregnancy; Pregnancy Complications, Cardiovascular
PubMed: 22789887
DOI: 10.1016/j.jacc.2012.03.048 -
American Journal of Physiology. Heart... Jan 2019Thoracic aortopathy, especially aneurysm, dissection, and rupture, is responsible for significant morbidity and mortality. Uncontrolled hypertension and aging are... (Review)
Review
Thoracic aortopathy, especially aneurysm, dissection, and rupture, is responsible for significant morbidity and mortality. Uncontrolled hypertension and aging are primary risk factors for such conditions, and they contribute to an increase in the mechanical stress on the wall and an increase in its structural vulnerability, respectively. Select genetic mutations also predispose to these lethal conditions, and the collection of known mutations suggests that dysfunctional mechanosensing and mechanoregulation of the extracellular matrix may contribute to pathogenesis and disease progression. In the absence of a well-accepted pharmacotherapy, nonsurgical treatments tend to focus on reducing the mechanical loading on the aorta, particularly via the use of antihypertensive medications and recommendations to avoid strenuous exercises such as weight lifting. In this brief review, we discuss the important effects of central artery stiffening on global hemodynamics and, in particular, on the increase in pulse pressure that acts on the proximal thoracic aorta. We consider Marfan syndrome as an illustrative aortopathy but discuss other conditions leading to thoracic aortic aneurysm and dissection. We highlight the importance of phenotyping the aorta biomechanically, not just clinically, and emphasize the utility of mouse models in elucidating molecular and mechanical mechanisms of disease. Notwithstanding the widely recognized role of central artery stiffening in driving end-organ disease, we suggest that there is similarly a need to consider its key role in thoracic aortopathy.
Topics: Animals; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Humans; Marfan Syndrome; Vascular Stiffness
PubMed: 30412443
DOI: 10.1152/ajpheart.00205.2018 -
Journal of Bone and Mineral Research :... May 2021Marfan syndrome (MFS), a rare genetic disease, has a prevalence of 6.5 in 100,000. Studies show that patients with MFS have reduced areal bone mineral density (BMD)...
Marfan syndrome (MFS), a rare genetic disease, has a prevalence of 6.5 in 100,000. Studies show that patients with MFS have reduced areal bone mineral density (BMD) compared with non-MFS individuals. We have previously shown that patients with MFS have reduced volumetric BMD and compromised trabecular and cortical bone microarchitecture. The present study was a registry-based, nationwide, population-based, cohort study using register data, aimed to evaluate fracture risk and fracture rates in MFS. We included 406 (196 women) patients with MFS through the Danish National Patient Register and 40,724 (19,327 women) persons, randomly selected and matched from the Civil Registry System. A total of 21.9% of the MFS and 18.9% of the reference population had experienced at least one fracture from 1995 to 2018. The fracture incidence rate was 27.5 per 1000 person-years in the MFS cohort (highest in young men and old women with MFS), and 20.3 per 1000 person-years in the reference population. The overall incidence rate ratio between the MFS and the reference population was 1.35 (95% confidence interval [CI ] 1.18-1.55) for all fractures. When evaluating the risk of being registered with an osteoporosis diagnosis in the Danish National Patient Register, starting relevant treatment for osteoporosis or experiencing a hip or spine fracture, 10.3% of the MFS cohort and 3.3% of the reference population could be classified as being osteoporotic. The between-group subhazard ratio was 3.97 (95% CI 2.56-6.25). Patients with MFS started treatment with an antiosteoporotic drug at a younger age than the reference population (57 [interquartile range 55-67] versus 71 [63-73]) years. The life expectancy in MFS is increasing, resulting in more patients facing diseases that are related to old age, such as age-related bone loss and increased risk of fractures. Our data suggest that bone health and fracture prevention needs to be part of the standard care for patients with MFS. © 2021 American Society for Bone and Mineral Research (ASBMR).
Topics: Aged; Bone Density; Cohort Studies; Female; Fractures, Bone; Humans; Male; Marfan Syndrome; Middle Aged; Osteoporosis
PubMed: 33567127
DOI: 10.1002/jbmr.4258 -
Respiration; International Review of... 2011Increased risk of spontaneous pneumothorax has been described in patients with Marfan syndrome and has been attributed, in part, to the presence of apical blebs and...
BACKGROUND
Increased risk of spontaneous pneumothorax has been described in patients with Marfan syndrome and has been attributed, in part, to the presence of apical blebs and bullae.
OBJECTIVES
We assess the risk of pneumothorax and its relationship to the presence of apical blebs and bullae in patients with Marfan syndrome in the era of CT imaging.
METHODS
A retrospective cohort study was performed of all patients 13 years or older with Marfan syndrome evaluated at the Mayo Clinic, Rochester, Minn., USA, from 1998 through 2008. One hundred and sixty-six patients met the current diagnostic criteria for Marfan syndrome and had chest imaging studies available for review.
RESULTS
The median age was 40 years (range 14-71); 37% had a smoking history. Eight of 166 patients (4.8%) had experienced 1 or more episodes of spontaneous pneumothorax, and 2 of these 8 patients had 2 or more episodes. Apical blebs or bullae were identified on radiologic imaging in 16 patients (9.6%). Four of 16 (25%) patients with apical blebs or bullae had a history of spontaneous pneumothorax compared to 4 of 150 patients (2.7%) without blebs or bullae (p = 0.003).
CONCLUSIONS
The frequency of blebs is relatively low in patients with Marfan syndrome but the risk of pneumothorax is significantly higher in those with radiologically detectable blebs or bullae. Chest CT scanning to identify blebs and bullae may allow risk stratification for pneumothorax in patients with Marfan syndrome.
Topics: Adolescent; Adult; Aged; Blister; Cohort Studies; Female; Humans; Male; Marfan Syndrome; Middle Aged; Pneumonectomy; Pneumothorax; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Young Adult
PubMed: 21252480
DOI: 10.1159/000322958 -
Heart (British Cardiac Society) Oct 1999To evaluate survival and complication free survival in patients with Marfan's syndrome and to assess the possible influence of recently revised guidelines for...
OBJECTIVE
To evaluate survival and complication free survival in patients with Marfan's syndrome and to assess the possible influence of recently revised guidelines for prophylactic aortic root replacement in these patients.
METHODS
130 patients who had been attending one institution over 14 years were evaluated. Kaplan-Meier analysis was performed in 125 patients who did not present with aortic root dissection as the first sign of Marfan's syndrome, with the end points: death, aortic root dissection, and prophylactic aortic root replacement after diagnosis. In the patients developing aortic root dissection, current guidelines for prophylactic aortic root replacement were retrospectively applied to investigate the number of dissections that could theoretically have been prevented. The guidelines were: (1) aortic root diameter >/= 55 mm, (2) positive family history of aortic dissections and aortic root diameter >/= 50 mm, and (3) aortic root growth >/= 2 mm/year. Outcomes following emergency surgery (15 patients) and prophylactic surgery of the aortic root (30 patients) were compared.
RESULTS
Five and 10 year survival after diagnosis was 95% and 88%, and the five and 10 year complication free survival was 78% and 66%, respectively. Thirteen patients developed dissection, 30 underwent prophylactic repair, and 82 had an uncomplicated course. Eleven dissections could theoretically have been prevented by application of the current guidelines. Five year survival following emergency and prophylactic repair of the aortic root was 51%, and 97%, respectively.
CONCLUSIONS
Survival in the Marfan's syndrome in the past 14 years seems satisfactory; with application of current guidelines, it has probably even improved. However, because of the high fatality rate in Marfan patients developing aortic root dissection, more extensive screening for Marfan's syndrome and a search for additional risk factors are desirable.
Topics: Adolescent; Adult; Aortic Dissection; Aortic Aneurysm; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Male; Marfan Syndrome; Middle Aged; Retrospective Studies; Risk Assessment; Survival Rate; Treatment Outcome
PubMed: 10490568
DOI: 10.1136/hrt.82.4.499 -
Revue Medicale de Liege Jul 2016The Marfan syndrome is a systemic connective tissue disorder with autosomal dominant inheritance. A mutation of the fibrillin-1 gene, a glycoprotein which is the main... (Review)
Review
The Marfan syndrome is a systemic connective tissue disorder with autosomal dominant inheritance. A mutation of the fibrillin-1 gene, a glycoprotein which is the main constituent of the extracellular matrix, is the cause of the disease. The cardinal features involve the skeletal, ocular and cardiovascular systems. The expression of the Marfan syndrome varies from the severe neonatal presentation to the classical manifestations of the child and young adult, but also comprises isolated features. In children, phenotypical manifestations are age dependent. For these reasons, the diagnosis of Marfan syndrome might be lately revealed by its cardiovascular complications. We report the case of 2 siblings: it illustrates the phenotypic variability that might be observed in a same family, the phenotype evolution with age and the diagnosis challenge in childhood.
Topics: Adolescent; Age Factors; Child; Female; Humans; Infant; Male; Marfan Syndrome
PubMed: 28383843
DOI: No ID Found