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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 -
American Journal of Medical Genetics.... Feb 2017The clinical manifestations of Marfan syndrome frequently cause pain. This study aimed to characterize pain in a cohort of adults with Marfan syndrome and investigate...
The clinical manifestations of Marfan syndrome frequently cause pain. This study aimed to characterize pain in a cohort of adults with Marfan syndrome and investigate demographic, physical, and psychological factors associated with pain and pain-related disability. Two hundred and forty-five participants (73% female, 89% non-Hispanic white, 90% North American) completed an online questionnaire assessing clinical features of Marfan syndrome, pain severity, pain-related disability, physical and mental health, depressive symptoms, pain catastrophizing, and insomnia. Eighty-nine percent of respondents reported having pain with 28% of individuals reporting pain as a presenting symptom of Marfan syndrome. Almost half of individuals reported that pain has spread from its initial site. Participants in our study reported poor physical and mental health functioning, moderate pain-related disability, and mild levels of depressive symptoms, sleep disturbances, and pain catastrophizing. Those who identified pain as an initial symptom of Marfan syndrome and those who reported that pain had spread from its initial site reported greater psychological burden compared with those without pain as an initial symptom or pain spreading. Physical health is the largest predictor of pain severity and pain-related disability. While pain catastrophizing and worse mental health functioning are significant correlates of pain severity and pain-related disability, respectively. Pain is a significant and persistent problem in Marfan syndrome and is associated with profound disability and psychological burden. Further studies are indicated to better characterize the directionality of pain, pain-related disability, and psychological burden in Marfan syndrome. © 2016 Wiley Periodicals, Inc.
Topics: Adolescent; Adult; Aged; Disabled Persons; Female; Humans; Male; Marfan Syndrome; Middle Aged; Neuropsychological Tests; Pain; Pain Measurement; Phenotype; Population Surveillance; Registries; Self Report; Severity of Illness Index; Surveys and Questionnaires; Young Adult
PubMed: 27862906
DOI: 10.1002/ajmg.a.38051 -
Orphanet Journal of Rare Diseases Dec 2015Marfan syndrome is a genetic disorder with considerable morbidity and mortality. Presently, clinicians use the 2010 revised Ghent nosology, which includes optional...
BACKGROUND
Marfan syndrome is a genetic disorder with considerable morbidity and mortality. Presently, clinicians use the 2010 revised Ghent nosology, which includes optional genetic sequencing of the FBN1 gene, to diagnose patients. So far, only a few studies based on older diagnostic criteria have reported a wide range of prevalence and incidence. Our aim was to study prevalence, incidence, and age at diagnosis in patients with Marfan syndrome.
METHOD
Using unique Danish patient-registries, we identified all possible Marfan syndrome patients recorded by the Danish healthcare system (1977-2014). Following, we confirmed or rejected the diagnosis according to the 2010 revised Ghent nosology.
RESULTS
We identified a total of 1628 persons with possible Marfan syndrome. We confirmed the diagnosis in 412, whereof 46 were deceased, yielding a maximum prevalence of 6.5/100,000 at the end of 2014. The annual median incidence was 0.19/100,000 (range: 0.0-0.7) which increased significantly with an incidence rate ratio of 1.03 (95% CI: 1.02-1.04, p < 0.001). We found a median age at diagnose of 19.0 years (range: 0.0-74). The age at diagnosis increased during the study period, uninfluenced by the changes in diagnostic criteria. We found no gender differences.
CONCLUSION
The increasing prevalence of Marfan syndrome during the study period is possibly due to build-up of a registry. Since early diagnosis is essential in preventing aortic events, diagnosing Marfan syndrome remains a task for both pediatricians and physicians caring for adults.
Topics: Adolescent; Adult; Age of Onset; Aged; Child; Child, Preschool; Denmark; Female; Fibrillin-1; Fibrillins; Humans; Incidence; Infant; Infant, Newborn; Male; Marfan Syndrome; Microfilament Proteins; Middle Aged; Prevalence; Registries; Young Adult
PubMed: 26631233
DOI: 10.1186/s13023-015-0369-8 -
Journal of Hypertension Jan 2018Marfan syndrome (MFS) is an autosomal dominant genetic disorder characterized by aortic root dilation and dissection and an abnormal fibrillin-1 synthesis. In this... (Observational Study)
Observational Study
OBJECTIVE
Marfan syndrome (MFS) is an autosomal dominant genetic disorder characterized by aortic root dilation and dissection and an abnormal fibrillin-1 synthesis. In this observational study, we evaluated aortic stiffness in MFS and its association with ascending aorta diameters and fibrillin-1 genotype.
METHODS
A total of 116 Marfan adult patients without history of cardiovascular surgery, and 144 age, sex, blood pressure and heart rate matched controls were enrolled. All patients underwent arterial stiffness evaluation through carotid-femoral pulse wave velocity (PWV) and central blood pressure waveform analysis (PulsePen tonometer). Fibrillin-1 mutations were classified based on the effect on the protein, into 'dominant negative' and 'haploinsufficient' mutations.
RESULTS
PWV and central pulse pressure were significantly higher in MFS patients than in controls [respectively 7.31 (6.81-7.44) vs. 6.69 (6.52-6.86) m/s, P = 0.0008; 41.3 (39.1-43.5) vs. 34.0 (32.7-35.3) mmHg, P < 0.0001], with a higher age-related increase of PWV in MFS (β 0.062 vs. 0.036). Pressure amplification was significantly reduced in MFS [18.2 (15.9-20.5) vs. 33.4 (31.6-35.2)%, P < 0.0001]. Central pressure profile was altered even in MFS patients without aortic dilatation. Multiple linear regression models showed that PWV independently predicted aortic diameters at the sinuses of Valsalva (ß = 0.243, P = 0.002) and at the sinotubular junction (ß = 0.186, P = 0.048). PWV was higher in 'dominant negative' than 'haploinsufficient' fibrillin-1 mutations [7.37 (7.04-7.70) vs. 6.60 (5.97-7.23) m/s, P = 0.035], although this difference was not significant after adjustment.
CONCLUSION
Aortic stiffness is increased in MFS, independently from fibrillin-1 genotype and is associated with diameters of ascending aorta. Alterations in central hemodynamics are present even when aortic diameter is within normal limits. Our findings suggest an accelerated arterial aging in MFS.
Topics: Adult; Aorta; Aortic Diseases; Arteries; Blood Pressure; Cross-Sectional Studies; Dilatation; Female; Fibrillin-1; Humans; Male; Marfan Syndrome; Middle Aged; Pulse Wave Analysis; Vascular Stiffness
PubMed: 29210860
DOI: 10.1097/HJH.0000000000001512 -
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 -
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 -
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