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Journal of the American College of... Jun 2021Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown.
BACKGROUND
Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown.
OBJECTIVES
The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis.
METHODS
MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up.
RESULTS
A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had >1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter.
CONCLUSIONS
Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.
Topics: Adult; Aortic Dissection; Aortic Aneurysm; Computed Tomography Angiography; Female; Follow-Up Studies; Humans; Male; Marfan Syndrome; Middle Aged; Risk Factors
PubMed: 34140103
DOI: 10.1016/j.jacc.2021.04.054 -
American Journal of Medical Genetics.... Nov 2021Tremendous progress has been made in understanding the etiology, pathogenesis, and treatment of inherited vascular connective tissue disorders. While new insights... (Review)
Review
Tremendous progress has been made in understanding the etiology, pathogenesis, and treatment of inherited vascular connective tissue disorders. While new insights regarding disease etiology and pathogenesis have informed patient counseling and care, there are numerous obstacles that need to be overcome in order to achieve the full promise of precision medicine. In this review, these issues will be discussed in the context of Marfan syndrome and Loeys-Dietz syndrome, with additional emphasis on the pioneering contributions made by Victor McKusick.
Topics: Connective Tissue; Connective Tissue Diseases; Humans; Loeys-Dietz Syndrome; Marfan Syndrome; Precision Medicine; Vascular Diseases
PubMed: 34428348
DOI: 10.1002/ajmg.a.62461 -
Journal of Pediatric Orthopedics. Part B May 2021We investigated the correlation between the musculoskeletal features and the cardiovascular anomalies in pediatric patients affected by Marfan syndrome, in order to...
We investigated the correlation between the musculoskeletal features and the cardiovascular anomalies in pediatric patients affected by Marfan syndrome, in order to identify possible orthopedic deformities that could be a warning sign for severe aortic dilatation. Moreover, we analyzed the role of the orthopedic aspects in the early diagnosis of the disease in a pediatric population. Seventy-two patients from 3 to 14 years of age, underwent interdisciplinary evaluation that included an orthopedic and cardiological examination. At the orthopedic examination, we analyzed the musculoskeletal features included in the systemic score of the revised Ghent criteria. Cardiological evaluation included a transthoracic echocardiography with definition of the cardiac Z-score, which is an index that evaluates aortic diameter. A statistical analysis was performed. We identified a statistically significant correlation between the presence of pectus excavatum and cardiac Z-score ≥3 (P = 0.022). Clinically, this data means that pectus excavatum is frequently observed in patients with larger aortic root diameter. On the contrary, no statistically significant correlation was found between the other investigated musculoskeletal features and a pathological Z-score. In the pediatric population, the diagnosis of Marfan syndrome remains difficult because many clinical manifestations are age-dependent and the Ghent criteria, usually used for adults, are not reliable in children. Our results show that the presence of pectus excavatum could help in the early identification of patients at greater risk of developing possibly fatal aortic disease. However, it is always indicated to screen all patients with Marfan syndrome for cardiac abnormalities, even in absence of pectus excavatum.
Topics: Adult; Child; Funnel Chest; Heart Defects, Congenital; Humans; Marfan Syndrome; Physical Examination
PubMed: 32932420
DOI: 10.1097/BPB.0000000000000798 -
Spine Deformity Jul 2022Spinal deformities present a common finding in patients affected with Marfan syndrome (MFS). More specifically, sagittal spine imbalances reflect the typical finding of...
INTRODUCTION
Spinal deformities present a common finding in patients affected with Marfan syndrome (MFS). More specifically, sagittal spine imbalances reflect the typical finding of such deformities. Observing spino-pelvic radiographs, we focused on eliciting any correlation between the pelvic incidence (PI), sacral slope (SS) and thoracolumbar kyphosis measurements, and categorising them according to a sagittal spinal classification system.
MATERIALS AND METHODS
One hundred seventy patient records were found over a 6 year period, and further refined to incorporate a total of 44 patients. 25 males and 19 females with an average age of 20 years at imaging. Electronic and hard copies of radiographs were used and measurements were made with virtual Cobb meters, rulers and protractors.
RESULTS
The mean PI was significantly different between type-I (46°) and type-II spines (35°) (p = 0.04), and the values for each class were as follows: type IA-53°, type IB-44°, type IC-36°, type IIA-42°, and type IIB-34°. Type II spines had a lower PI compared to type IA spines (p = 0.037) and to that of an unaffected population. Statistically significant differences were noted in SS between groups (t test; p < 0.001), and ANOVA demonstrated that the largest differences between spinal classes were found in SS.
CONCLUSION
In our study, PI values were much higher in type I compared to type II spines. Type II spines had PI values as expected, however, had higher than expected SS values. SS followed a down trending pattern across all spinal classes. Type IIA spines had a much greater preponderance for male patients. Overall, we wish to highlight in particular that type II spines were associated with a much lower PI and SS, and report these differences in pelvic morphology and sagittal spine patterns seen in MFS patients. The pelvic tilt and sacral slope parameters observed in our Type II spines may further reflect and characterize the deformity.
Topics: Adult; Female; Humans; Kyphosis; Male; Marfan Syndrome; Posture; Sacrum; Scoliosis; Young Adult
PubMed: 35277839
DOI: 10.1007/s43390-022-00484-x -
International Journal of Molecular... Feb 2022Fibrillin-1 is the major structural component of the 10 nm-diameter microfibrils that confer key physical and mechanical properties to virtually every tissue, alone and... (Review)
Review
Fibrillin-1 is the major structural component of the 10 nm-diameter microfibrils that confer key physical and mechanical properties to virtually every tissue, alone and together with elastin in the elastic fibers. Mutations in fibrillin-1 cause pleiotropic manifestations in Marfan syndrome (MFS), including dissecting thoracic aortic aneurysms, myocardial dysfunction, progressive bone loss, disproportionate skeletal growth, and the dislocation of the crystalline lens. The characterization of these MFS manifestations in mice, that replicate the human phenotype, have revealed that the underlying mechanisms are distinct and organ-specific. This brief review summarizes relevant findings supporting this conclusion.
Topics: Animals; Disease Models, Animal; Fibrillin-1; Humans; Marfan Syndrome; Mice; Mutation; Organ Specificity
PubMed: 35163812
DOI: 10.3390/ijms23031892 -
The Journal of Thoracic and... Jul 2023
Commentary: Tissue may not be the issue in patients with Marfan syndrome and acute type A aortic dissection: Lessons from the German Registry for Acute Aortic Dissection Type A.
Topics: Humans; Marfan Syndrome; Aortic Dissection
PubMed: 34517984
DOI: 10.1016/j.jtcvs.2021.08.052 -
American Journal of Cardiovascular... Nov 2021Thoracic aortic dilatation often has an asymptomatic course but may present with lethal complications such as aortic rupture or dissection, particularly when the... (Review)
Review
Thoracic aortic dilatation often has an asymptomatic course but may present with lethal complications such as aortic rupture or dissection, particularly when the thoracic aorta is aneurysmally enlarged; therefore, appropriate diagnosis, surveillance, and management are vital. Recommendations regarding imaging and surgical management are outlined in contemporary clinical practice guidelines. Dedicated guidelines regarding medical therapies for the management of thoracic aortic dilatation are lacking. Most of the medical treatment strategies, especially recommendations regarding pharmacological medical therapies related to β-blockade and angiotensin receptor blockers, are derived from data on patients with Marfan syndrome. The main aims of medical therapies for the management of thoracic aortic dilatation are (1) to control the progression of the disease, and (2) to prevent complications related to the disease (such as aortic dissection and mortality). This paper reviews the contemporary evidence and highlights the gaps in evidence to be investigated in further studies.
Topics: Adult; Aorta, Thoracic; Aortic Diseases; Dilatation, Pathologic; Humans; Marfan Syndrome
PubMed: 33748919
DOI: 10.1007/s40256-021-00472-y -
Current Opinion in Cardiology May 2024This review aims to delineate the genetic basis of Marfan syndrome (MFS) and underscore the pivotal role of genetic testing in the diagnosis, differential diagnosis,... (Review)
Review
PURPOSE OF REVIEW
This review aims to delineate the genetic basis of Marfan syndrome (MFS) and underscore the pivotal role of genetic testing in the diagnosis, differential diagnosis, genotype-phenotype correlations, and overall disease management.
RECENT FINDINGS
The identification of pathogenic or likely pathogenic variants in the FBN1 gene, associated with specific clinical features such as aortic root dilatation or ectopia lentis, is a major diagnostic criterion for MFS. Understanding genotype-phenotype correlations is useful for determining the timing of follow-up, guiding prophylactic aortic root surgery, and providing more precise information to patients and their family members during genetic counseling. Genetic testing is also relevant in distinguishing MFS from other conditions that present with heritable thoracic aortic diseases, allowing for tailored and individualized management.
SUMMARY
Genetic testing is essential in different steps of the MFS patients' clinical pathway, starting from the phase of diagnosis to management and specific treatment.
Topics: Humans; Marfan Syndrome; Phenotype; Mutation; Fibrillin-1; Genetic Testing
PubMed: 38386349
DOI: 10.1097/HCO.0000000000001126 -
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 -
Bone Jun 2020Marfan syndrome (MFS) is an autosomal genetic disorder of connective tissue, due to alterated fibrillin-1. The aim of our study was to verify the rate of fractures in...
Marfan syndrome (MFS) is an autosomal genetic disorder of connective tissue, due to alterated fibrillin-1. The aim of our study was to verify the rate of fractures in children with MFS in correlation to bone mineral density and compare the prevalence to the general population in the same latitude. We enrolled 80 patients (37 girls and 43 boys) with the diagnosis of Marfan syndrome, median age 10 y (3 to 17 years). Fracture occurrence was inferred from medical records of patients with MFS. Bone mineral density (BMD) was measured at lumbar spine, femoral neck and total femur by dual-energy x-ray absorptiometry. BMD values were expressed as z-scores, and adjusted for height using height-for-age z-scores. Bone turnover markers and vitamin D were measured. We assessed incidence of fracture in general pediatric population of our geographic area (45°N latitude). A total of 24 fractures were recorded in 21 patients (15 boys and 6 girls), involving both short and long bones, due to mild or moderate trauma. An incidence estimate has been calculated for each year, and an average incidence of 29.2/1000 MFS patients was obtained, markedly higher (P=0.034) than the incidence of fracture calculated in the same geographical area in pediatric patients (15.8/1000). We did not detect differences in anthropometric measurements, BMD values and biochemical indices between patients who fractured and patients who did not. Similarly, no differences were found between patients on losartan therapy and patients not in treatment for the same variables. In conclusion, the incidence of fractures was higher in patients with MFS compared to general population of the same age and latitude. The management of MFS must account bone status health and start strategies of fracture prevention.
Topics: Absorptiometry, Photon; Adolescent; Bone Density; Child; Female; Femur Neck; Fractures, Bone; Humans; Male; Marfan Syndrome
PubMed: 32222606
DOI: 10.1016/j.bone.2020.115333