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Biomolecules Sep 2022Fibrillin-1 is an extracellular matrix protein that assembles into microfibrils that provide critical functions in large blood vessels and other tissues. Mutations in...
Fibrillin-1 is an extracellular matrix protein that assembles into microfibrils that provide critical functions in large blood vessels and other tissues. Mutations in the fibrillin-1 gene are associated with cardiovascular, ocular, and skeletal abnormalities in Marfan syndrome. Fibrillin-1 is a component of the wall of large arteries but has been poorly described in other vessels. We examined the microvasculature in the retina using wild type mice and two models of Marfan syndrome, and . In the mouse retina, fibrillin-1 was detected around arterioles, in close contact with the basement membrane, where it colocalized with MAGP1. Both a mutation in fibrillin-1 or fibrillin-1 underexpression characteristically altered the microvasculature. In and mice, arterioles were enlarged with reduced MAGP1 deposition and focal loss of smooth muscle cell coverage. Losartan, which prevents aortic enlargement in mice, prevented smooth muscle cell loss and vessel leakiness when administrated in a preventive mode. Moreover, losartan also partially rescued the defects in a curative mode. Thus, fibrillin-1/MAGP1 performs essential functions in arteriolar integrity and mutant fibrillin-1-induced defects can be prevented or partially rescued pharmacologically. These new findings could have implications for people with Marfan syndrome.
Topics: Mice; Animals; Fibrillin-1; Marfan Syndrome; Fibrillins; Losartan; Arterioles; Microfilament Proteins; Extracellular Matrix Proteins; Retina
PubMed: 36291539
DOI: 10.3390/biom12101330 -
Medicine Dec 2023Connective tissue disorders, including Marfan syndrome (MS) and Ehlers-Danlos syndrome (EDS), are characterized by genetic mutations affecting connective tissue... (Review)
Review
Connective tissue disorders, including Marfan syndrome (MS) and Ehlers-Danlos syndrome (EDS), are characterized by genetic mutations affecting connective tissue structural integrity. These disorders significantly elevate the risk of aortic dissection, a life-threatening condition. This comprehensive review delves into the intricate interplay between connective tissue disorders and aortic dissection, shedding light on the clinical features, pathophysiology, genetic underpinnings, diagnostic approaches, clinical management, associated comorbidities, and prognosis, mainly focusing on MS and EDS, while also exploring rare connective tissue disorders and forms of cutis laxa contributing to aortic pathology.
Topics: Humans; Connective Tissue Diseases; Marfan Syndrome; Ehlers-Danlos Syndrome; Aortic Aneurysm; Aortic Dissection; Connective Tissue
PubMed: 38050214
DOI: 10.1097/MD.0000000000036499 -
Anesthesiology Clinics Dec 2022Thoracic aortic aneurysms and thoracoabdominal aneurysms are often found incidentally. Complications include dissection or rupture. Most of the thoracic aortic aneurysms... (Review)
Review
Thoracic aortic aneurysms and thoracoabdominal aneurysms are often found incidentally. Complications include dissection or rupture. Most of the thoracic aortic aneurysms and thoracoabdominal aneurysms develop in patients with risk factors for atherosclerosis. Younger patients without significant cardiovascular risk factors may have a genetic basis and include syndromes such as Marfan, Ehlers-Danlos, and Loeys-Dietz and bicuspid aortic valve. Most thoracic aneurysms grow slowly over time and factors that accelerate growth rate include dissection, aneurysm size, bicuspid valve disease, and Marfan syndrome. Size cutoffs where complications occur determine when surgery or intervention should be considered.
Topics: Humans; Aortic Aneurysm, Thoracic; Aortic Dissection; Marfan Syndrome; Heart Valve Diseases; Risk Factors
PubMed: 36328622
DOI: 10.1016/j.anclin.2022.08.011 -
European Heart Journal Nov 2020
Topics: Angiotensin II Type 1 Receptor Blockers; Follow-Up Studies; Humans; Losartan; Marfan Syndrome; Transcription Factors
PubMed: 32607591
DOI: 10.1093/eurheartj/ehaa418 -
Child's Nervous System : ChNS :... Feb 2024Spinal deformities are common in Marfan syndrome (MFS). They usually involve the thoraco-lumbar spine but rarely involves the cervical spine. Kyphosis is the common... (Review)
Review
BACKGROUND
Spinal deformities are common in Marfan syndrome (MFS). They usually involve the thoraco-lumbar spine but rarely involves the cervical spine. Kyphosis is the common spine deformity of the cervical spine and mandates surgical correction as they are at risk of neurological deterioration since they are refractory to conservative management. Few studies of surgical correction of spine deformity included cervical deformity.
OBJECTIVES
To analyze the challenges faced during surgery, clinical and radiological outcome, and complications following surgical correction for cervical kyphosis in Marfan syndrome.
METHODS
We identified that 5 patients with a diagnosis of MFS with cervical kyphosis who underwent fusion surgery between the years 2010 and 2022 were reviewed, retrospectively. We analyzed the demographic details, radiological parameters, operative variables (blood loss and nuances), perioperative complications, length of stay, clinical and radiological outcome, and complications following fusion surgery for cervical kyphosis in MFS.
RESULTS
The mean age of patients was 16.6 ± 4.72 years (range, 12-23 years). The average kyphotic vertebra involved is 3 ± 0.7 bodies (range 2-4) with 2 patients with thoracic deformity. All patients underwent surgical deformity correction. All patients improved clinically with Nurick grade (pre vs. post: 3.4 vs. 2.2) and mJOA (pre vs. post: 8.2 vs. 12.6). There was significant deformity correction from 37.48° to 9.1°. Mean blood loss encountered was 900 ± 173.2 ml. Perioperative complications: wound complication with CSF leak (1). Late complications: ventilator dependence (1) and junctional kyphosis (1). Mean length of hospital stay was 103 ± 178.9 days. All patients were doing symptomatically better after mean follow-up of 58 ± 28.32 months. One patient is bedridden and hospitalized.
CONCLUSION
Cervical kyphosis is a rare spine deformity in patients with MFS, and they usually present with neurological deterioration mandating surgical correction. Multidisciplinary approach (pediatrics, genetics and cardiology) is required for systematic evaluation of these patients. They should be evaluated with necessary imaging to rule out associated spinal deformity (atlanto-axial subluxation, scoliosis, and intraspinal pathology like ductal ectasia). Our results suggest better surgical outcome in terms of low operative complications with neurologic improvement in MFS patients. These patients require regular follow-up to identify late complications (instrument failure, non-union, and pseudarthrosis).
Topics: Humans; Child; Adolescent; Young Adult; Adult; Marfan Syndrome; Retrospective Studies; Treatment Outcome; Kyphosis; Cervical Vertebrae; Spinal Fusion
PubMed: 37391518
DOI: 10.1007/s00381-023-06046-4 -
Quality of Life Research : An... Dec 2022Marfan syndrome (MFS) is a connective tissue disorder that affects skeletal, ocular, pulmonary, cardiovascular, and central nervous systems. Symptoms may lead to...
PURPOSE
Marfan syndrome (MFS) is a connective tissue disorder that affects skeletal, ocular, pulmonary, cardiovascular, and central nervous systems. Symptoms may lead to diminished quality of life (QoL) in individuals with MFS compared with healthy individuals. Currently, there is little evidence regarding the impact of MFS on swallowing and QoL. This study examined perceptions of swallowing difficulties and QoL among persons with MFS.
METHOD
A total of 356 participants (1% response rate) with a self-reported diagnosis of MFS provided medication regime and completed a Quality-of-Life Index and a modified version of the SWAL-QOL used to assess 8 QOL concepts related to swallowing: burden, duration, desire, food choice, fear, mental health, social concerns, and fatigue.
RESULTS
Dysphagia symptoms were reported by 62% (N = 356) of the participants. Analyses assessing correlations between responses to SWAL-QOL questions, QoL scores, and reported medications were conducted. Further, responses on the SWAL-QOL predicted QoL satisfaction, even after controlling for medications. Findings revealed that greater swallowing difficulty affects QoL satisfaction and overall QoL, but not QoL importance. Further, specific medications were associated with differences in swallowing difficulty as well as QoL satisfaction.
CONCLUSIONS
The findings of the current study suggest that individuals with MFS may experience specific swallowing difficulties which impact QoL. Specific classes of drugs may also be associated with reported swallowing QoL and QoL satisfaction in MFS. These findings have implications for clinicians who work with individuals with MFS.
Topics: Humans; Deglutition; Quality of Life; Cross-Sectional Studies; Marfan Syndrome; Surveys and Questionnaires; Deglutition Disorders
PubMed: 35867322
DOI: 10.1007/s11136-022-03192-1 -
The Journal of Thoracic and... Jul 2022The aim of this study was to disclose the differences of surgical outcomes between Marfan syndrome with mutations in fibrillin-1 gene and Loeys-Dietz syndrome with...
OBJECTIVE
The aim of this study was to disclose the differences of surgical outcomes between Marfan syndrome with mutations in fibrillin-1 gene and Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2.
METHODS
We reviewed 368 patients aged less than 50 years who underwent surgery for thoracic aortic diseases between 1988 and 2019, and enrolled 99 patients with Marfan syndrome (26.9%; 57 men, 33 ± 7.5 years) and 24 patients with Loeys-Dietz syndrome (6.5%; 13 men, 28 ± 11 years).
RESULTS
Freedom from all causes of mortality was similar between the 2 groups (P = .40, log-rank). The cumulative incidence of reintervention was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P = .016, Gray). The cumulative incidence of first aortic arch reoperation for aortic arch aneurysm was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P < .001, Gray). The cumulative incidence of first aortic root reoperation for aortic root aneurysm (P = .57, Gray) and first descending aorta reoperation for descending aortic aneurysm (P = .76, Gray) was similar between the 2 groups. The cumulative incidence of aortic dissection after initial surgery was significantly lower in Marfan syndrome than in Loeys-Dietz syndrome (P = .0059, Gray).
CONCLUSIONS
Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2 revealed higher rates of reoperation, and more specifically the arch reoperation was higher in those with Loeys-Dietz syndrome than those with Marfan syndrome. Aggressive arch surgery in the initial operation on the proximal aorta is recommendable in Loeys-Dietz syndrome to avoid additional aortic events. In Marfan syndrome, this is controversial in patients without dissection because of a low possibility to expand.
Topics: Adolescent; Adult; Aortic Dissection; Aorta; Female; Humans; Loeys-Dietz Syndrome; Male; Marfan Syndrome; Receptor, Transforming Growth Factor-beta Type I; Receptor, Transforming Growth Factor-beta Type II; Young Adult
PubMed: 32891455
DOI: 10.1016/j.jtcvs.2020.07.089 -
Cardiology in the Young Dec 2021To determine whether racial/ethnic differences exist for the treatment of Marfan syndrome aortopathy. The 2014 Pediatric Heart Network randomised trial of losartan...
OBJECTIVE
To determine whether racial/ethnic differences exist for the treatment of Marfan syndrome aortopathy. The 2014 Pediatric Heart Network randomised trial of losartan versus atenolol in Marfan syndrome paediatric and young adult patients showed no treatment differences in the rate of aortic root growth over 3 years; however, they did not examine racial/ethnic differences, and recent data suggest that angiotensin receptor blockers may have different pharmacologic effects in different racial/ethnic populations.
METHODS
We performed a secondary analysis of public-use data from the Pediatric Heart Network randomised trial comparing the differences by race/ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic patients) amongst the treatment groups for the primary outcome of rate of aortic root enlargement by z score and secondary outcome of rate of change of absolute diameter of aortic root, z score and absolute diameter of ascending aorta, and blood pressure changes.
RESULTS
For aortic root enlargement by z score amongst non-Hispanic White patients, patients on losartan exhibited an annual z score change of -0.090 ± 0.016, compared to -0.146 ± 0.015 for those on atenolol (p = 0.01), favouring atenolol. For Hispanic and non-Hispanic Black patients, there was no difference in primary or secondary outcomes between treatment groups.
CONCLUSION
Non-Hispanic White patients had a small, but statistically significantly greater decrease in aortic root z score favouring atenolol over losartan. There were no significant differences amongst Hispanic or non-Hispanic Black patients, which may be due to relatively small size numbers. These findings may have important implications for medication selection by race/ethnicity in Marfan syndrome patients, which has not previously been evaluated in studies.
Topics: Angiotensin II Type 1 Receptor Blockers; Aorta; Atenolol; Child; Humans; Losartan; Marfan Syndrome; Young Adult
PubMed: 33845931
DOI: 10.1017/S104795112100130X -
Orphanet Journal of Rare Diseases Oct 2020Aortic root dilatation and-dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic...
BACKGROUND
Aortic root dilatation and-dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality.
METHODS
To characterize myocardial dysfunction and arrhythmia in MFS we conducted a prospective longitudinal case-control study including 86 patients with MFS (55.8% women, mean age 36.3 yr-range 13-70 yr-) and 40 age-and sex-matched healthy controls. Cardiac ultrasound, resting and ambulatory ECG (AECG) and NT-proBNP measurements were performed in all subjects at baseline. Additionally, patients with MFS underwent 2 extra evaluations during 30 ± 7 months follow-up. To study primary versus secondary myocardial involvement, patients with MFS were divided in 2 groups: without previous surgery and normal/mild valvular function (MFS-1; N = 55) and with previous surgery or valvular dysfunction (MFS-2; N = 31).
RESULTS
Compared to controls, patients in MFS-1 showed mild myocardial disease reflected in a larger left ventricular end-diastolic diameter (LVEDD), lower TAPSE and higher amount of (supra) ventricular extrasystoles [(S)VES]. Patients in MFS-2 were more severely affected. Seven patients (five in MFS-2) presented decreased LV ejection fraction. Twenty patients (twelve in MFS-2) had non-sustained ventricular tachycardia (NSVT) in at least one AECG. Larger LVEDD and higher amount of VES were independently associated with NSVT.
CONCLUSION
Our study shows mild but significant myocardial involvement in patients with MFS. Patients with previous surgery or valvular dysfunction are more severely affected. Evaluation of myocardial function with echocardiography and AECG should be considered in all patients with MFS, especially in those with valvular disease and a history of cardiac surgery.
Topics: Adult; Arrhythmias, Cardiac; Cardiomyopathies; Case-Control Studies; Female; Humans; Male; Marfan Syndrome; Prospective Studies
PubMed: 33097072
DOI: 10.1186/s13023-020-01581-8 -
Clinical & Experimental Ophthalmology Dec 2019To determine visual and surgical results in children with Marfan syndrome.
IMPORTANCE
To determine visual and surgical results in children with Marfan syndrome.
BACKGROUND
Marfan syndrome involves ocular complications which can lead to visual disturbance and amblyopia. Data about the visual and surgical results in children with Marfan syndrome is vital for the clinical management of these patients.
DESIGN
Retrospective data analysis.
PARTICIPANTS
Eighty-two eyes of 41 patients with a genetically proved diagnosis of Marfan syndrome.
METHODS
Medical records of patients with Marfan syndrome were reviewed between 2007 and 2017. Ocular complications, visual acuity (VA) of patients with/without lensectomy and surgical method were evaluated.
MAIN OUTCOME MEASURES
VA outcomes of patients with Marfan syndrome with/without surgical repair of ectopia lentis.
RESULTS
In 27 (66%) of the 41 patients a bilateral subluxation of the lens was visible and 14 (52%) patients received lensectomy. The mean age at initial presentation was 12.3 ± 9 years and mean follow-up was 3 years (range 1-7). VA varied from 1.2 to -0.1 logMAR at first examination. At initial presentation, mean VA was 0.1 ± 0.7 logMAR in patients with a normal lens status (n = 14) and 0.3 ± 0.5 logMAR in patients with subluxation of the lens (n = 27) (P < .01). VA improved from 0.2 ± 0.5 logMAR to 0.1 ± 0.5 logMAR (P = .06) in children with subluxation of the lens who did not need a lensectomy (n = 12) and from 0.5 ± 0.5 logMAR to 0.2 ± 0.5 logMAR (P = .02) in patients who were referred to lensectomy with/without secondary lens implantation.
CONCLUSIONS AND RELEVANCE
In Marfan syndrome subluxation of the lens was found in the majority of children. Improvement of VA resulted in children with subluxation of the lens and following lensectomy.
Topics: Child; Child, Preschool; Ectopia Lentis; Female; Follow-Up Studies; Humans; Infant; Male; Marfan Syndrome; Myopia; Ophthalmologic Surgical Procedures; Retrospective Studies; Time Factors; Treatment Outcome; Visual Acuity
PubMed: 31325202
DOI: 10.1111/ceo.13596