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The New England Journal of Medicine Sep 2017
Topics: Aged; Ectopia Lentis; Female; Humans; Iris; Marfan Syndrome
PubMed: 28902597
DOI: 10.1056/NEJMicm1615424 -
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 -
Archives of Disease in Childhood Apr 2007In recent years, there have been many advances in the treatment of cardiac disease in children with Marfan's syndrome. Early diagnosis, meticulous echocardiographic... (Review)
Review
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 signalling and the potential treatment role of TGFbeta antagonists may lead to exciting new treatments, but the results of clinical trials are awaited. In managing the cardiovascular complications of Marfan's syndrome, the paediatrician has to walk a difficult path. On the one hand, restrictive lifestyle advice and drugs may need to be prescribed, often in the context of a family history of major surgery or even sudden death. On the other hand, it is essential to encourage the often asymptomatic child to develop and mature as normally as possible.
Topics: Adrenergic beta-Antagonists; Aortic Valve; Dilatation, Pathologic; Female; Heart Defects, Congenital; Heart Valve Prosthesis Implantation; Humans; Infant; Infant, Newborn; Marfan Syndrome
PubMed: 17376944
DOI: 10.1136/adc.2006.097469 -
Genetics in Medicine : Official Journal... Aug 2019Life expectancy for a person with Marfan syndrome has essentially doubled over the past four decades. During this period, the clinical histories of the organs managed... (Review)
Review
Life expectancy for a person with Marfan syndrome has essentially doubled over the past four decades. During this period, the clinical histories of the organs managed routinely have improved, and will continue to be. Prominent examples are the eyes, the heart and aorta, and some features of the skeletal system. Meanwhile, the natural histories of organ systems that have not been subjected to treatment need to be described. This is particularly important as due to the improved life span many symptoms and organ systems are only recently being recognized as being intrinsic to Marfan syndrome. Examples are the distal aorta and peripheral arteries, ventricular function, the central nervous system, sleep apnea, and adiposity. As a result, each person with Marfan syndrome will need to be evaluated and followed by more specialists than previously. Moreover, the coordinator of diagnostic testing and clinical referral must be aware of the expanded phenotype as people with Marfan syndrome age and the importance of life-long management of classical and novel features. The benefits of increased longevity and its consequences need to be addressed by investigators, health-care providers, and patients alike.
Topics: Aorta; Central Nervous System; Eye; Heart; Humans; Life Expectancy; Longevity; Marfan Syndrome; Skeleton
PubMed: 30573797
DOI: 10.1038/s41436-018-0399-4 -
British Journal of Pharmacology Apr 2022Recent studies have shown that NO is a central mediator in diseases associated with thoracic aortic aneurysm, such as Marfan syndrome. The progressive dilation of the... (Review)
Review
Recent studies have shown that NO is a central mediator in diseases associated with thoracic aortic aneurysm, such as Marfan syndrome. The progressive dilation of the aorta in thoracic aortic aneurysm ultimately leads to aortic dissection. Unfortunately, current medical treatments have neither halt aortic enlargement nor prevented rupture, leaving surgical repair as the only effective treatment. There is therefore a pressing need for effective therapies to delay or even avoid the need for surgical repair in thoracic aortic aneurysm patients. Here, we summarize the mechanisms through which NO signalling dysregulation causes thoracic aortic aneurysm, particularly in Marfan syndrome. We discuss recent advances based on the identification of new Marfan syndrome mediators related to pathway overactivation that represent potential disease biomarkers. Likewise, we propose iNOS, sGC and PRKG1, whose pharmacological inhibition reverses aortopathy in Marfan syndrome mice, as targets for therapeutic intervention in thoracic aortic aneurysm and are candidates for clinical trials.
Topics: Aortic Dissection; Animals; Aorta; Aortic Aneurysm; Aortic Aneurysm, Thoracic; Cyclic GMP-Dependent Protein Kinase Type I; Humans; Marfan Syndrome; Mice
PubMed: 34599830
DOI: 10.1111/bph.15694 -
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 -
Revista Medica de Chile Nov 2006Marfan Syndrome is an autosomic dominant genetic disorder of the elastic fibers of connective tissue. Although neonatal and infant forms of the disease exist, the... (Review)
Review
Marfan Syndrome is an autosomic dominant genetic disorder of the elastic fibers of connective tissue. Although neonatal and infant forms of the disease exist, the classic Marfan Syndrome is the most frequent form of presentation in childhood and adolescence, with a hereditary background in 70 to 85% of cases. Due to the natural evolution of the disease, there is a progressive involvement of different organs or systems such as skeletal, cardiovascular, dura, ocular, skin-integument and lungs. However, the suspicion must arise on skeletal clinical aspects which are first evident signs. The cardiovascular involvement appears later but is the major life threatening complication. When suspecting Marfan phenotype, it is mandatory to apply Ghent criteria based on family history and clinical findings to establish the diagnosis. If diagnosis is confirmed, the severity of organ involvement must be assessed, to take preventive and/or therapeutic measures, including the search of new cases among relatives. When patients do not fulfill the diagnostic criteria, they must have a yearly evaluation considering the natural progressive evolution of the disease. The aim of this review is to spread and unify criteria on this disease whose diagnosis is eminently clinical, that requires early integral and updated management by a multidisciplinary group, to obtain the best quality of life and survival.
Topics: Adolescent; Adult; Child; Child, Preschool; Diagnosis, Differential; Humans; Infant; Infant, Newborn; Marfan Syndrome; Phenotype; Prognosis
PubMed: 17277858
DOI: 10.4067/s0034-98872006001100014 -
Acta Ophthalmologica May 2022The aim of the present study was to investigate photophobia and disability glare in adult patients with Marfan syndrome (MFS).
PURPOSE
The aim of the present study was to investigate photophobia and disability glare in adult patients with Marfan syndrome (MFS).
METHODS
In this case-control study, 44 patients with MFS (87 eyes) were compared to 44 controls (88 eyes), who were matched for age and sex. The subjects were asked to grade their photophobia and glare using 10-cm visual analogue scales (VAS), which were marked with 'never' at zero and 'always' at 10 -cm. In addition, disability glare was measured with C-Quant straylight meter.
RESULTS
The patients with MFS had significantly higher VAS scores than the controls in four out of seven statements related to photophobia and glare. When including cataract, spherical equivalent, iris colour, axial length and corneal curvature, three of the seven statements were still significantly different between the two groups. The mean straylight values were 1.29 ± 0.03 log(s) in the MFS group and 1.01 ± 0.03 log(s) in the control group (p < 0.001, mixed model). These differences remained significant after adjusting for cataract, spherical equivalent, iris colour, axial length and corneal curvature.
CONCLUSION
Patients with MFS reported more photophobia and had a higher straylight value than the control group. Awareness of these findings of more photophobia and glare in the MFS patients is important when counselling and treating these patients.
Topics: Adult; Case-Control Studies; Cataract; Glare; Humans; Light; Marfan Syndrome; Photophobia; Scattering, Radiation; Visual Acuity
PubMed: 34173343
DOI: 10.1111/aos.14935 -
American Journal of Medical Genetics.... Jan 2021Marfan syndrome (MFS) is a multisystemic, autosomal dominant connective tissue disorder that occurs de novo in 25%. In many families, parent and child(ren) are affected,...
Marfan syndrome (MFS) is a multisystemic, autosomal dominant connective tissue disorder that occurs de novo in 25%. In many families, parent and child(ren) are affected, which may increase distress in parents. To assess distress, 42 mothers (29% MFS) and 25 fathers (60% MFS) of 43 affected children, completed the validated screening-questionnaire Distress thermometer for parents of a chronically ill child, including questions on overall distress (score 0-10; ≥4 denoting "clinical distress") and everyday problems (score 0-36). Data were compared to 1,134 control-group-parents of healthy children. Mothers reported significantly less overall distress (2, 1-4 vs. 3, 1-6; p = .049; r = -.07) and total everyday problems (3, 0-6 vs. 4, 1-8; p = .03; r = -.08) compared to control-group-mothers. Mothers without MFS reported significantly less overall distress compared to mothers with MFS, both of a child with MFS (1, 0-4 vs. 3.5, 2-5; p = .039; r = -.17). No significant differences were found between the father-groups, nor between the group of healthy parents of an affected child living together with an affected partner compared to control-group-parents. No differences in percentages of clinical distress were reported between mothers and control-group-mothers (33 vs. 42%); fathers and control-group-fathers (28 vs. 32%); nor between the other groups. Distress was not associated with the children's MFS characteristics. Concluding, parents of a child with MFS did not show more clinical distress compared to parents of healthy children. However, clinical distress was reported in approximately one-third and may increase in case of acute medical complications. We advise monitoring distress in parents of a child with MFS to provide targeted support.
Topics: Adult; Anxiety; Child; Child, Preschool; Chronic Disease; Depression; Fathers; Female; Humans; Male; Marfan Syndrome; Mothers; Parenting; Parents; Quality of Life; Stress, Psychological; Surveys and Questionnaires
PubMed: 33034422
DOI: 10.1002/ajmg.a.61906 -
Acta Ophthalmologica Sep 2022The main objective of this study was to examine the pupillary response in patients with Marfan syndrome (MFS) and secondarily to determine whether changes in the...
PURPOSE
The main objective of this study was to examine the pupillary response in patients with Marfan syndrome (MFS) and secondarily to determine whether changes in the pupillary response are associated with the increased disability glare previously shown in the same patient population.
METHODS
This study included 60 eyes of 34 patients with MFS diagnosed in accordance with the Ghent-2 criteria and 81 eyes of 44 controls. Pupillary response was measured with a pupillograph and disability glare with a straylight meter.
RESULTS
The patients with MFS had a significantly smaller maximum pupil size than the control group, 4.87 (4.50-5.23) mm versus 5.58 (5.25-5.90) mm (p = 0.01). In addition, they exhibited slower contraction velocities (p = 0.03) and longer re-dilation times (p = 0.01) compared with the control group. The mean straylight value was higher in patients with MFS than controls, even when including pupillary parameters together with lens surgery, cataract, iris colour, axial length and corneal curvature as possible explanatory variables in the analysis. However, when including data from both groups, a significant negative correlation was seen between maximum pupillary diameter and straylight value (p = 0.01). The other pupillary parameters did not correlate with straylight.
CONCLUSION
Patients with MFS had a smaller maximum pupil diameter, slower pupillary contraction and longer re-dilation time than the controls. Despite the correlation between pupil size and straylight value, the pupillary response demonstrated in MFS eyes could not explain the increased straylight in these patients.
Topics: Adult; Glare; Humans; Light; Marfan Syndrome; Pupil; Scattering, Radiation
PubMed: 34890490
DOI: 10.1111/aos.15079