scholarly journals How to Distinguish Marfan Syndrome from Marfanoid Habitus in a Physical Examination—Comparison of External Features in Patients with Marfan Syndrome and Marfanoid Habitus

2022 ◽  
Vol 19 (2) ◽  
pp. 772
Author(s):  
Lidia Wozniak-Mielczarek ◽  
Michalina Osowicka ◽  
Alicja Radtke-Lysek ◽  
Magda Drezek-Nojowicz ◽  
Natasza Gilis-Malinowska ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Positive Likelihood Ratio ◽  
Red Flags ◽  
High Prevalence ◽  
Age Dependent ◽  
Fibrillin 1 ◽  
Systemic Disorder ◽  
Study Population ◽  
Hindfoot Deformity

Marfan Syndrome (MFS) is a systemic disorder caused by mutations in fibrillin-1. The most common cause of mortality in MFS is dissection and rupture of the aorta. Due to a highly variable and age-dependent clinical spectrum, the diagnosis of MFS still remains sophisticated. The aim of the study was to determine if there exist phenotypic features that can play the role of “red flags” in cases of MFS suspicion. The study population included 306 patients (199 children and 107 adults) who were referred to the Department of Pediatric Cardiology due to suspicion of MFS. All patients underwent complete clinical evaluation in order to confirm the diagnosis of MFS according to the modified Ghent criteria. MFS was diagnosed in 109 patients and marfanoid habitus in 168 patients. The study excluded 29 patients with other hereditary thoracic aneurysm syndromes. Comparative analysis between patients with Marfan syndrome and marfanoid habitus was performed. Symptoms with high prevalence and high positive likelihood ratio were identified (pectus carinatum, reduced elbow extension, hindfoot deformity, gothic palate, downslanting palpebral fissures, lens subluxation, myopia ≥ 3 dioptres remarkably high stature). The differentiation between patients with MFS and marfanoid body habitus is not possible by only assessing external body features; however, “red flags” could be helpful in the screening phase.

scholarly journals A Case of Neonatal Marfan Syndrome: A Management Conundrum and the Role of a Multidisciplinary Team

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Elliott J. Carande ◽  
Samuel J. Bilton ◽  
Satish Adwani
Keyword(s):  
Marfan Syndrome ◽  
Surgical Intervention ◽  
Rare Condition ◽  
Mitral Valve Regurgitation ◽  
Left Ventricular ◽  
Cardiac Complications ◽  
Chromosome 15 ◽  
Fibrillin 1 ◽  
Neonatal Marfan Syndrome

Neonatal Marfan syndrome (nMFS) is a rare condition with a poor prognosis. It is genotypically and phenotypically distinct from the typical Marfan syndrome and carries a poorer prognosis. This case report describes the progression of a 14-month-old girl diagnosed with nMFS at 5 months of age. Her diagnosis followed the identification of a fibrillin-1 mutation (FBN1gene, exon 26, chromosome 15), which is a common locus of nMFS. This patient developed severe cardiac complications resulting in congestive cardiac failure in early life and required major cardiac surgery. Since surgical intervention, our patient is still reliant on a degree of ventilator support, but the patient has gained weight and echocardiography has demonstrated improved left ventricular function and improved tricuspid and mitral valve regurgitation. Therefore, we argue the importance of a cautious multidisciplinary approach to early surgical intervention in cases of nMFS.

scholarly journals Marfan Syndrome: A Case Report

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Rajendran Ganesh ◽  
Rajendran Vijayakumar ◽  
Haridoss Selvakumar
Keyword(s):  
Stainless Steel ◽  
Case Report ◽  
Connective Tissue ◽  
Blood Vessel ◽  
Marfan Syndrome ◽  
Autosomal Dominant ◽  
The Body ◽  
Tissue Protein ◽  
Fibrillin 1 ◽  
Systemic Disorder

Marfan syndrome is an autosomal dominant systemic disorder of the connective tissue. Children affected by the Marfan syndrome carry a mutation in one of their two copies of the gene that encodes the connective tissue protein fibrillin-1. Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and the large blood vessel that distributes blood from the heart to the rest of the body. A case report of Marfan syndrome has been reported with oral features. The dental problems of the child were treated under general anesthesia and a one-month review showed intact stainless steel crowns' restorations and no signs of secondary caries.

scholarly journals Losartan Increases Survival of the Fbn1mgR/mgR Mouse Model of Marfan Syndrome in an Age-Dependent Manner

2021 ◽  
Author(s):  
Jeffrey D. Smith ◽  
Jeff Z. Chen ◽  
Rebecca Phillips ◽  
Alan Daugherty ◽  
Mary B. Sheppard
Keyword(s):  
Marfan Syndrome ◽  
Angiotensin Receptor Blockers ◽  
Primary Objective ◽  
Dependent Manner ◽  
Wild Type ◽  
Age Dependent ◽  
Fibrillin 1 ◽  
Receptor Blockers ◽  
To Receive ◽  
Overall Mortality

AbstractClinical trials investigating angiotensin receptor blockers (ARB) for attenuation of thoracic aortic aneurysm in people with Marfan syndrome have demonstrated variable efficacy. The primary objective of this study was to determine whether the age of mice at the time of losartan initiation affected mortality in fibrillin-1 hypomorphic (Fbn1mgR/mgR) mice. Male (n=40) and female (n=28) Fbn1mgR/mgR mice were randomized to receive losartan in drinking water (0.6 g/L) starting at either 24 or 50 days of age. Controls included Fbn1mgR/mgR mice (20M, 14F) and wild type (15M, 15F) littermates who were not administered the drug. Mortality of Fbn1mgR/mgR males receiving losartan at postnatal day 24 (P24) was not different from wild type controls (p=0.138). Survival of Fbn1mgR/mgR males administered losartan at P50 was not different compared to Fbn1mgR/mgR males receiving no drug (p=0.194) and decreased compared to wild type mice (p=0.002). Survival analysis after P50 demonstrated increased survival of Fbn1mgR/mgR males administered losartan at P50 compared to Fbn1mgR/mgR mice receiving no drug (p=0.017). Age is a critical variable that affects the therapeutic efficacy of losartan in male Fbn1mgR/mgR mice. Since overall mortality in female Fbn1mgR/mgR mice was lower than in male Fbn1mgR/mgR mice, a survival benefit with losartan was not detected in females.

scholarly journals Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias

2021 ◽  
Vol 12 ◽  
Author(s):  
Pauline Arnaud ◽  
Zakaria Mougin ◽  
Catherine Boileau ◽  
Carine Le Goff
Keyword(s):  
Marfan Syndrome ◽  
Wide Spectrum ◽  
Genetic Data ◽  
Mirror Image ◽  
Pathogenic Mechanism ◽  
Unique Combination ◽  
Multisystem Disease ◽  
Fibrillin 1 ◽  
Joint Limitation

The term “fibrillinopathies” gathers various diseases with a wide spectrum of clinical features and severity but all share mutations in the fibrillin genes. The first described fibrillinopathy, Marfan syndrome (MFS), is a multisystem disease with a unique combination of skeletal, thoracic aortic aneurysm (TAA) and ocular features. The numerous FBN1 mutations identified in MFS are located all along the gene, leading to the same pathogenic mechanism. The geleophysic/acromicric dysplasias (GD/AD), characterized by short stature, short extremities, and joint limitation are described as “the mirror image” of MFS. Previously, in GD/AD patients, we identified heterozygous FBN1 mutations all affecting TGFβ-binding protein-like domain 5 (TB5). ADAMTS10, ADAMTS17 and, ADAMTSL2 are also involved in the pathogenic mechanism of acromelic dysplasia. More recently, in TAA patients, we identified mutations in THSD4, encoding ADAMTSL6, a protein belonging to the ADAMTSL family suggesting that ADAMTSL proteins are also involved in the Marfanoid spectrum. Together with human genetic data and generated knockout mouse models targeting the involved genes, we provide herein an overview of the role of fibrillin-1 in opposite phenotypes. Finally, we will decipher the potential biological cooperation of ADAMTS-fibrillin-1 involved in these opposite phenotypes.

scholarly journals Orthopaedic Aspects of Marfan Syndrome: The Experience of a Referral Center for Diagnosis of Rare Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Fernando De Maio ◽  
Alessandro Fichera ◽  
Vincenzo De Luna ◽  
Federico Mancini ◽  
Roberto Caterini
Keyword(s):  
Marfan Syndrome ◽  
Acute Aortic Dissection ◽  
Thoracolumbar Kyphosis ◽  
Height Ratio ◽  
Ectopia Lentis ◽  
Arm Span ◽  
Acetabular Protrusion ◽  
Fibrillin 1 ◽  
Hindfoot Deformity ◽  
Emergent Surgery

Marfan syndrome is caused by mutations in the fibrillin-1 gene (FBN1). The most important features affect the cardiovascular system, eyes, and skeleton. The aim of this study was to report the most frequent musculoskeletal alterations observed in 146 patients affected by Marfan syndrome. Fifty-four patients (37%) underwent cardiac surgery and 11 of them received emergent surgery for acute aortic dissection. Ectopia lentis was found in 68 patients (47%) whereas myopia above 3D occurred in 46 patients (32%). Musculoskeletal anomalies were observed in all patients with Marfan syndrome. In 88 patients (60.2%), the associated “wrist and thumb sign” was present; in 58 patients (39.7%), pectus carinatum deformity; in 44 patients (30.1%), pectus excavatum; in 49 patients (33.5%), severe flatfoot; in 31 patients (21.2%), hindfoot deformity; in 54 patients (36.9%), reduced US/LS ratio or increased arm span-height ratio; in 37 patients (25.3%), scoliosis or thoracolumbar kyphosis; in 22 patients (15%), reduced elbow extension (170° or less). Acetabular protrusion was ascertained on radiographs in 27 patients (18.4%). Orthopaedic aspects of the disease are very important for an early diagnosis; however, we have not observed definite correlations between the extent of orthopaedic involvement and aortic complications.

scholarly journals Clinical relevance of genotype–phenotype correlations beyond vascular events in a cohort study of 1500 Marfan syndrome patients with FBN1 pathogenic variants

2021 ◽  
Author(s):  
Pauline Arnaud ◽  
Olivier Milleron ◽  
Nadine Hanna ◽  
Jacques Ropers ◽  
Nadia Ould Ouali ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Phenotypic Variability ◽  
Premature Termination Codon ◽  
Connective Tissue Disorder ◽  
Vascular Events ◽  
Severe Scoliosis ◽  
Pathogenic Variants ◽  
Fibrillin 1 ◽  
Cysteine Content

Abstract Purpose Marfan syndrome (MFS) is a connective tissue disorder in which several systems are affected with great phenotypic variability. Although known to be associated with pathogenic variants in the FBN1 gene, few genotype–phenotype correlations have been found in proband studies only. Methods In 1,575 consecutive MFS probands and relatives from the most comprehensive database worldwide, we established survival curves and sought genotype–phenotype correlations. Results A risk chart could be established with clinical and genetic data. Premature termination codon variants were not only associated with a shorter life expectancy and a high lifelong risk of aortic event, but also with the highest risk of severe scoliosis and a lower risk for ectopia lentis (EL) surgery. In-frame variants could be subdivided according to their impact on the cysteine content of fibrillin-1 with a global higher severity for cysteine loss variants and the highest frequency of EL surgery for cysteine addition variants. Conclusion This study shows that FBN1 genotype–phenotype correlations exist for both aortic and extra-aortic features. It can be used for optimal risk stratification of patients with a great importance for genetic counseling and personalized medicine. This also provides additional data for the overall understanding of the role of fibrillin-1 in various organs.

scholarly journals AB0008 THE IMPACT OF STAT4 RS7574865, IL6 RS1800795, IL6R RS2228145 AND RS4845618 ON RHEUMATOID ARTHRITIS SUSCEPTIBILITY IN BELARUSIAN POPULATION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1307.1-1308
Author(s):  
E. Siniauskaya ◽  
T. Kuzhir ◽  
V. Yagur ◽  
R. Goncharova
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Donors ◽  
Genetic Model ◽  
Online Tool ◽  
Genotype Frequencies ◽  
Systemic Disorder ◽  
Autoimmune Pathogenesis ◽  
The Impact ◽  
Arthritis Susceptibility

Background:Rheumatoid arthritis (RA) is a chronic systemic disorder of the connective tissue of still unknown aetiology and complex autoimmune pathogenesis that primarily affects small joints. HLA alleles provide for 11-37% of the RA heritability, suggesting the substantial role of the non-HLA loci in genetic predisposition to RA. Among non-HLA loci,IL6, IL6RandSTAT4genes attract attention, however, the data concerning their influence on RA risk are somewhat contradictory.Objectives:The aim of the study was to analyze the involvement of four SNPs (STAT4rs7574865,IL6rs1800795,IL6Rrs2228145 and rs4845618) in RA susceptibility.Methods:187 patients diagnosed with RA (mean age 58.2 ± 11.9), and 380 healthy blood donors (mean age 37.18 ± 10.69 years) were included into the study. DNA extraction from peripheral blood samples was performed using the phenol-chloroform method. SNPs were genotyped using the real-time PCR with fluorescent probes. The allele and genotype frequencies were compared using the χ2 test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the VassarStats online tool.Results:Utilizing recessive genetic model we found an association between TT genotype ofSTAT4rs7574865 (OR = 2.362; 95%CI [1.0378 – 5.376], p = 0.038) and RA. ForIL6rs1800795, it was found that CC genotype had significantly higher frequency among patients with rheumatoid arthritis as compared to that in controls (OR = 1.52; 95%CI [1.02 – 2.27], p = 0.0456). No associations ofIL6Rrs2228145 and rs4845618 SNPs with risk of RA were found in the total group of patients vs. controls. It was also shown thatIL6rs1800795 CC genotype frequency was significantly higher among the patients with RF-negative status (p = 0.0019).Conclusion:Thus, we provide evidence for association of theSTAT4rs7574865 andIL6rs1800795 variants with risk of RA in the Belarusian population, some features of interplay being revealed between gene polymorphisms analyzed and RA antibody status. Abovementioned SNPs may contribute to RA genetic susceptibility in the Belarusian population.Disclosure of Interests:None declared

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