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Archives of Oral Biology Aug 2020The role of this study is to highlight a correlation between patients with Marfan syndrome and oral health status by evaluating and reviewing the relevant scientific... (Review)
Review
INTRODUCTION
The role of this study is to highlight a correlation between patients with Marfan syndrome and oral health status by evaluating and reviewing the relevant scientific literature. The syndrome is characterized by an abnormal production of the fibrillin1 protein. The manifestations of Marfan syndrome affect organs that contain connective tissue such as the skeletal system, the eyes, the heart and the blood vessels, the lungs and the fibrous membranes that cover the brain and the spine. The facial bony and soft structures can therefore be affected, influencing the stage of tooth formation and the structure of the teeth, we also want to analyze in this study, the periodontal complications and the management of the latter, with the use of surgical techniques that include the use of biomaterials.
MATERIALS AND METHODS
A comprehensive review of the literature was conducted according to PRISMA guidelines. After a careful analysis of the work obtained by two independent academics, there have been 18. All data from the studies were compared and many of these highlighted the presence of abnormalities in the oral district.
RESULTS
The studies taken into consideration a whole series of oral manifestations related to the Marfan syndrome. Oral mucosa, periodontal, dental abnormalities, bone abnormalities or joint dysfunction are frequently involved in patients affected by this disease.
CONCLUSIONS
All the research have given positive results in terms of dental or oral anomalies. This information may be essential to limit and intervene early improving the oral health of syndromic patients.
Topics: Humans; Marfan Syndrome; Oral Health
PubMed: 32446937
DOI: 10.1016/j.archoralbio.2020.104745 -
Arteriosclerosis, Thrombosis, and... Sep 2023Transmural failure of the aorta is responsible for substantial morbidity and mortality; it occurs when mechanical stress exceeds strength. The aortic root and ascending...
BACKGROUND
Transmural failure of the aorta is responsible for substantial morbidity and mortality; it occurs when mechanical stress exceeds strength. The aortic root and ascending aorta are susceptible to dissection and rupture in Marfan syndrome, a connective tissue disorder characterized by a progressive reduction in elastic fiber integrity. Whereas competent elastic fibers endow the aorta with compliance and resilience, cross-linked collagen fibers confer stiffness and strength. We hypothesized that postnatal reductions in matrix cross-linking increase aortopathy when turnover rates are high.
METHODS
We combined ex vivo biaxial mechanical testing with multimodality histological examinations to quantify expected age- and sex-dependent structural vulnerability of the ascending aorta in Marfan versus wild-type mice without and with 4-week exposures to β-aminopropionitrile, an inhibitor of lysyl oxidase-mediated cross-linking of newly synthesized elastic and collagen fibers.
RESULTS
We found a strong β-aminopropionitrile-associated sexual dimorphism in aortic dilatation in Marfan mice and aortic rupture in wild-type mice, with dilatation correlating with compromised elastic fiber integrity and rupture correlating with compromised collagen fibril organization. A lower incidence of rupture of β-aminopropionitrile-exposed Marfan aortas associated with increased lysyl oxidase, suggesting a compensatory remodeling of collagen that slows disease progression in the otherwise compromised aorta.
CONCLUSIONS
Collagen fiber structure and function in the Marfan aorta are augmented, in part, by increased lysyl oxidase in female and especially male mice, which improves structural integrity, particularly via fibrils in the adventitia. Preserving or promoting collagen cross-linking may represent a therapeutic target for an otherwise vulnerable aorta.
Topics: Animals; Female; Male; Mice; Aminopropionitrile; Collagen; Dilatation; Disease Models, Animal; Extracellular Matrix; Fibrillin-1; Marfan Syndrome; Mice, Inbred C57BL; Protein-Lysine 6-Oxidase
PubMed: 37470181
DOI: 10.1161/ATVBAHA.123.319122 -
American Journal of Medical Genetics.... Jan 2022Abnormalities of the capillaries of the digits in hereditary hemorrhagic telangiectasia can be detected by shining through a narrow beam of light through the dorsal side...
Abnormalities of the capillaries of the digits in hereditary hemorrhagic telangiectasia can be detected by shining through a narrow beam of light through the dorsal side and visualizing the vasculature on the palmar side, a procedure termed transillumination. This study was performed to determine if this method can detect digital vascular abnormalities in aortopathies and arteriopathies. Transillumination was performed in patients with Marfan syndrome (MFS), thoracic aortic aneurysm and dissection (TAAD), vascular Ehlers-Danlos syndrome (vEDS), bicuspid aortic valve with aortopathy, and arteriopathies without aortopathy. Subjects with no known vascular disorders were controls. Digital vascular abnormalities were present in some patients with all of the disorders and were especially frequent in MFS, TAAD, and vEDS. All patients had significantly more digital vascular abnormalities than control subjects. Transillumination can detect vascular abnormalities in digits of patients with a variety of conditions with aortopathy or arteriopathy.
Topics: Aortic Dissection; Ehlers-Danlos Syndrome; Humans; Marfan Syndrome; Telangiectasia, Hereditary Hemorrhagic; Transillumination
PubMed: 34529342
DOI: 10.1002/ajmg.a.62495 -
Cardiology in Review 2020Marfan Syndrome (MFS) is an autosomal dominant, genetically inherited connective tissue disorder which primarily affects the cardiovascular system, but can also have... (Review)
Review
Marfan Syndrome (MFS) is an autosomal dominant, genetically inherited connective tissue disorder which primarily affects the cardiovascular system, but can also have systemic manifestations. First described in 1896, MFS has a prevalence of around 1/5000 in the general population. It is becoming increasingly common to see patients with MFS in a clinical setting due to the improved care of patients with adult congenital heart disease and general improvement in survival. Mortality, however, remains high largely due to the risk of aortic dissection as a result of the aortic root dilatation frequently seen in these patients. Contemporary management has therefore been focused on imaging-based surveillance to prevent these catastrophic events and intervene surgically in a timely manner. However, it is increasingly recognized that some patients do suffer aortic dissection below the expected threshold for surgical intervention. With this in mind, there has been interest in the role of biomarkers as an adjunct to imaging in the care of these patients. This article will provide an overview of the literature on potential biomarkers studied so far in MFS, as well as potential future directions.
Topics: Aortic Dissection; Biomarkers; Humans; Marfan Syndrome
PubMed: 31985522
DOI: 10.1097/CRD.0000000000000289 -
Pediatrics Apr 2023Marfan syndrome is a heritable connective tissue disorder that affects many different organ systems. In some cases, features of Marfan syndrome can be recognized at...
Marfan syndrome is a heritable connective tissue disorder that affects many different organ systems. In some cases, features of Marfan syndrome can be recognized at birth, but the majority will have manifestations that emerge throughout childhood and into adulthood. Significant morbidity and mortality are associated with this syndrome, and its features are best managed using a multidisciplinary approach. This clinical report is designed to assist the pediatrician in recognizing the features of Marfan syndrome as well as caring for the individual with Marfan syndrome to maximize their health and quality of life.
Topics: Infant, Newborn; Humans; Child; Adolescent; Marfan Syndrome; Quality of Life; Pediatricians
PubMed: 36938616
DOI: 10.1542/peds.2023-061450 -
Heart Failure Clinics Jan 2022The inherited connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome [LDS], and Ehlers-Danlos syndrome [EDS]) involve connective tissue of various organ... (Review)
Review
The inherited connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome [LDS], and Ehlers-Danlos syndrome [EDS]) involve connective tissue of various organ systems. These pathologies share many common features, nonetheless compared to Marfan syndrome, LDS' cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis. The EDS are currently classified into thirteen subtypes. There is substantial symptoms overlap between the EDS subtypes, and they are associated with an increased incidence of cardiovascular abnormalities, such as mitral valve prolapse and aortic dissection.
Topics: Humans; Loeys-Dietz Syndrome; Marfan Syndrome; Myocardium
PubMed: 34776077
DOI: 10.1016/j.hfc.2021.07.007 -
American Journal of Medical Genetics.... Feb 2023To optimize care for children with Marfan syndrome (MFS) in the Netherlands, Dutch MFS growth charts were constructed. Additionally, we aimed to investigate the effect...
To optimize care for children with Marfan syndrome (MFS) in the Netherlands, Dutch MFS growth charts were constructed. Additionally, we aimed to investigate the effect of FBN1 variant type (haploinsufficiency [HI]/dominant negative [DN]) on growth, and compare MFS-related height increase across populations. Height and weight data of individuals with MFS aged 0-21 years were retrospectively collected. Generalized Additive Models for Location, Scale and Shape (GAMLSS) was used for growth chart modeling. To investigate genotype-phenotype relationships, FBN1 variant type was included as an independent variable in height-for-age and BMI-for-age models. MFS-related height increase was compared with that of previous MFS growth studies from the United States, Korea, and France. Height and weight data of 389 individuals with MFS were included (210 males). Height-for-age, BMI-for-age, and weight-for-height charts reflected the tall and slender MFS habitus throughout childhood. Mean increase in height of individuals with MFS compared with the general Dutch population was significantly lower than in the other three MFS populations compared to their reference populations. FBN1-HI variants were associated with taller height in both sexes, and decreased BMI in females (p-values <0.05). This Dutch MFS growth study broadens the notion that genetic background and MFS variant type (HI/DN) influence tall and slender stature in MFS.
Topics: Male; Female; Humans; Marfan Syndrome; Growth Charts; Retrospective Studies; Netherlands; Mutation; Genotype; Phenotype; Fibrillin-1
PubMed: 36380655
DOI: 10.1002/ajmg.a.63047 -
International Journal of Molecular... Oct 2023Marfan syndrome (MFS) is a connective tissue disorder caused by gene mutations leading to TGF-β signaling hyperactivation, vascular wall weakness, and thoracic aortic...
Marfan syndrome (MFS) is a connective tissue disorder caused by gene mutations leading to TGF-β signaling hyperactivation, vascular wall weakness, and thoracic aortic aneurysms (TAAs). The pathogenetic mechanisms are not completely understood and patients undergo early vascular surgery to prevent TAA ruptures. We previously reported miR-632 upregulation in MFS TAA tissues compared with non-genetic TAA tissues. DNAJB6 is a gene target of miR-632 in cancer and plays a critical role in blocking epithelial-to-mesenchymal transition by inhibiting the Wnt/β catenin pathway. TGF-β signaling also activates Wnt/β catenin signaling and induces endothelial-to-mesenchymal transition (End-Mt) and fibrosis. We documented that miR-632 upregulation correlated with DNAJB6 expression in both the endothelium and the tunica media of MFS TAA ( < 0.01). Wnt/β catenin signaling, End-Mt, and fibrosis markers were also upregulated in MFS TAA tissues ( < 0.05, < 0.01 and < 0.001). Moreover, miR-632 overexpression inhibited , inducing Wnt/β catenin signaling, as well as End-Mt and fibrosis exacerbation ( < 0.05 and < 0.01). TGF-β1 treatment also determined miR-632 upregulation ( < 0.01 and < 0.001), with the consequent activation of the aforementioned processes. Our study provides new insights about the pathogenetic mechanisms in MFS aortopathy. Moreover, the high disease specificity of miR-632 and DNAJB6 suggests new potential prognostic factors and/or therapeutic targets in the progression of MFS aortopathy.
Topics: Humans; Marfan Syndrome; beta Catenin; Fibrosis; Transforming Growth Factor beta; MicroRNAs; Nerve Tissue Proteins; Molecular Chaperones; HSP40 Heat-Shock Proteins
PubMed: 37894814
DOI: 10.3390/ijms242015133 -
EMBO Molecular Medicine Jan 2024Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), a disease caused by fibrillin-1 gene mutations....
Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition associated with Marfan syndrome (MFS), a disease caused by fibrillin-1 gene mutations. While various conditions causing TAAD exhibit aortic accumulation of the proteoglycans versican (Vcan) and aggrecan (Acan), it is unclear whether these ECM proteins are involved in aortic disease. Here, we find that Vcan, but not Acan, accumulated in Fbn1 aortas, a mouse model of MFS. Vcan haploinsufficiency protected MFS mice against aortic dilation, and its silencing reverted aortic disease by reducing Nos2 protein expression. Our results suggest that Acan is not an essential contributor to MFS aortopathy. We further demonstrate that Vcan triggers Akt activation and that pharmacological Akt pathway inhibition rapidly regresses aortic dilation and Nos2 expression in MFS mice. Analysis of aortic tissue from MFS human patients revealed accumulation of VCAN and elevated pAKT-S473 staining. Together, these findings reveal that Vcan plays a causative role in MFS aortic disease in vivo by inducing Nos2 via Akt activation and identify Akt signaling pathway components as candidate therapeutic targets.
Topics: Animals; Humans; Mice; Aortic Aneurysm, Thoracic; Aortic Diseases; Aortic Dissection; Azides; Deoxyglucose; Marfan Syndrome; Nitric Oxide Synthase Type II; Proto-Oncogene Proteins c-akt; Versicans
PubMed: 38177536
DOI: 10.1038/s44321-023-00009-7 -
Journal of AAPOS : the Official... Oct 2023To investigate the population-based incidence and de novo mutation rate of Marfan syndrome and risk of ectopia lentis.
PURPOSE
To investigate the population-based incidence and de novo mutation rate of Marfan syndrome and risk of ectopia lentis.
METHODS
Patients newly diagnosed with Marfan syndrome in Olmsted County, Minnesota, from January 1, 1976, through December 31, 2005, were identified through medical records review. Outcome measures were Marfan incidence, de novo mutation rate, risk of ectopia lentis.
RESULTS
Marfan syndrome was identified in 17 patients during the 30-year period, yielding an incidence of 0.52 per 100,000 people/year (95% CI, 0.27-0.77). Mean age at diagnosis was 24.4 years (range, 1.7 year to 51.3 years). Nine patients (53%) were female. Of the 17, 5 (29%) were new mutations, with a calculated mutation rate of 3.8 ± 1.7 × 10. Four (24%) were diagnosed with ectopia lentis, including 3 at the time of their Marfan diagnosis. Of the 14 patients at risk for developing ectopia lentis after being diagnosed with Marfan syndrome, 1 (7%) developed it during a mean follow-up of 9 years (range, 0-6.4). Twelve (71%) were diagnosed with dilated ascending aorta during a mean follow-up of 13.2 years (range, 6.7 months to 28.9 years).
CONCLUSIONS
Incidence and de novo mutation rate of Marfan syndrome in this population-based cohort was higher than prior reports. Ectopia lentis, whose prevalence in North America has not been reported previously, occurred in approximately one-fourth of study patients and more commonly around the time of initial Marfan diagnosis.
Topics: Humans; Female; Infant; Male; Ectopia Lentis; Marfan Syndrome; Mutation Rate; Incidence; Mutation
PubMed: 37716433
DOI: 10.1016/j.jaapos.2023.07.006