Pupillary capture following sutureless scleral-fixated intraocular lens in children with Marfan syndrome

AIM:To compare the clinical outcomes between two approaches for sutureless scleral-fixated intraocular lens(SFIOL)in children with Marfan syndrome(MFS).METHODS:The study included 15 children(26 eyes)with lens subluxation due to MFS.These children underwent lensectomy,anterior vitrectomy,and sutureless SFIOL.According to the position of placement of intraocular lens(IOL)haptics,two study groups were reviewed for best corrected visual acuity(BCVA)and postoperative complications:group A,14 eyes with haptics fixated at 2.0 mm from the limbus;group B,12 eyes with the haptics fixated at 2.5 mm from the limbus.RESULTS:The mean axial length for all patients was 25.66±2.35 mm.Postoperative BCVA in logMAR were significant improved in both groups(0.77±0.32 to 0.17±0.12 in group A,0.66±0.25 to 0.24±0.12 in group B,both P<0.001)while no significant difference between two groups(P>0.05).Pupillary capture was main postoperative complication,occurring between 3d and 18mo.It occurred in 7 eyes in group A and one eye in group B(P=0.02).CONCLUSION:Sutureless SFIOL is an effective treatment approach for lens subluxation in children with MFS.Pupillary capture is the main postoperative complication.Fixated IOL haptics at 2.5 mm from the limbus can reduce the occurrence of pupillary capture.

Transseptal approach for catheter ablation of left-sided accessory pathways in children with Marfan syndrome:A case report

BACKGROUND Left-sided accessory pathways(APs)can be accessed with either a transaortic(TA)or transseptal approach(TS).For children with Marfan syndrome(MFS)who have aortic disease,the use of TA can aggravate the disease,making TS the best choice for these patients.CASE SUMMARY A 10-year-old girl was hospitalized because of intermittent heart palpitations and chest tightness.She was diagnosed with MFS,supraventricular tachycardia,Wolff-Parkinson-White syndrome,and left-sided AP was detected by cardiac electrophysiological.Catheter ablation was successfully performed via TS under the guidance of the Ensite system.During the follow-up,no recurrence or complications occurred.CONCLUSION The TS for catheter ablation of left-sided APs can be considered in children with MFS.Adequate evaluation and selection of the appropriate puncture site are particularly important.

Individualized antiarrhythmic drug regimen in Marfan syndrome:a case study

Marfan syndrome(MFS)includes a serious organic heart disease,for which no effective treatment methods are currently available.Most available drugs are only for symptoms management and have significant side effects.This study reported on the efficacy of a combination of Chinese and Western medicines to treat arrhythmia in a patient with MFS.The patient was a young woman who was frequently treated with amiodarone owing to MFS-related organic changes in her heart.Considering the negative side effects of amiodarone in the patient,a combination of traditional Chinese medicine decoction,Wenxin granule,and metoprolol was used to gradually replace amiodarone treatment.After three months of treatment the patient’s premature ventricular beats were controlled,and follow-up results were satisfactory.This case study provides a reference for the treatment of premature ventricular beats in patients with organic changes due to MFS.

Summary of Home Nursing for Lens Dislocation Among Patients with Marfan Syndrome

Marfan syndrome is a rare genetic disease,and the condition of most patients deteriorates with age.The lesions are mainly cardiovascular,skeletal,and ocular lesions.Its clinical manifestations are characterized by congenital heart disease,ectopic lens,slender body,slender limbs,spider fingers(toes),and general muscle dysplasia.In the early stage of this disease,when the symptoms are not yet clearly manifested,some patients came to the hospital for treatment due to decreased vision.According to the particularity of crystal dislocation patients with Marfan syndrome,this article provides home nursing education in terms of physiological and psychological aspects,and builds an effective home nursing model to promote the physical and mental recovery of patients.

Novel pharmacological strategies to prevent aortic complications in Marfan syndrome

The Marfan syndrome(MFS)is a systemic connective tissue disorder caused by mutations in the FBN1 gene.Recent molecular studies,most performed in mouse models,revealed that the MFS is more a developmental abnormality with broad and complex effects on the morphogenesis and function of multiple organ systems.FBN1 haploinsufficiency and dysregulated transforming growth factor-beta(TGF-β)signaling seem to be critical for clinical manifestations in MFS including aortic root dilatation.Aortic root aneurysm and aortic dissection represent the main causes of morbidity and mortality in MFS.Most importantly,TGF-βantagonism through angiotensin II type 1 receptor blockers(ARBs),for example losartan,has been shown to prevent and possibly reverse aortic root dilatation in a mouse model of MFS.A first human study on a small pediatric cohort confirmed those promising results in reducing the aortic root growth over a follow-up period of 12 to 47 months.So,a large multicenter trial has been set up and results should be available soon.Other therapeutic strategies which might be combined with losartan include traditionalβ-blockade,doxycyclin and statins.Such management could offer the first potential for primary prevention of clinical manifestations in MFS.

The ASD that Wouldn’t Go Away:An Unusual Case of ASD Device Failure in a Patient with Marfan Syndrome

Marfan syndrome patients have connective tissue abnormalities that predispose them to intracardiac defects and postoperative complications.We present a case of late onset ASD device failure secondary to device movement within the atrial septum in a girl with Marfan syndrome.This case study suggests that further studies are necessary to determine the optimal device and approach for ASD repair in this patient cohort.

Acute inferior wall myocardial infarction induced by aortic dissection in a young adult with Marfan syndrome:A case report

BACKGROUND Aortic dissection(AD)is an emergent and life-threatening disorder,and its inhospital mortality was reported to be as high as 24.4%-27.4%.AD can mimic other more common disorders,especially acute myocardial infarction(AMI),in terms of both symptoms and electrocardiogram changes.Reperfusion for patients with AD may result in catastrophic outcomes.Increased awareness of AD can be helpful for early diagnosis,especially among younger patients.CASE SUMMARY We report a 28-year-old man with acute left side chest pain without cardiovascular risk factors.He was diagnosed with acute inferior ST-segment elevation myocardial infarction(STEMI),which,based on illness history,physical examination,and intraoperative findings,was eventually determined to be type A AD caused by Marfan syndrome.Emergent coronary angiography revealed the anomalous origin of the right coronary artery as well as eccentric stenosis of the proximal segment.Subsequently,computed tomography angiography(CTA)showed intramural thrombosis of the ascending aorta.Finally,the patient was transferred to the cardiovascular surgery department for a Bentall operation.He was discharged 13 d after the operation,and aortic CTA proved a full recovery at the 2-year follow-up.CONCLUSION It is essential and challenging to differentiate AD from AMI.Type A AD should be the primary consideration in younger STEMI patients without cardiovascular risk factors but with outstanding features of Marfan syndrome.

Identifi cation of Three FBN1 Mutations in Chinese Patients with Typical or Incomplete Marfan Syndrome by Whole-Exome Sequencing

Objective:The purpose of this work was to obtain the phenotypes and detect potential mutations in three Chinese patients with Marfan syndrome(MFS)or incomplete MFS phenotypes.Methods:Three unrelated patients with a defi nite or suspected clinical diagnosis of MFS and their family members were recruited for research.Genomic DNA was extracted from peripheral blood of these patients and their family members.All the exons were sequenced by next-generation sequencing and the variants were further validated by Sanger sequencing.The functional consequences of the mutations were analyzed with various genomic resources and bioinformatics tools.Results:Three FBN1 mutations were identifi ed in the three patients,including one novel mutation(2125G>A)and two previously reported mutations(4786C>T and 6325C>T).It was interesting to note that the parents of these patients were normal as assessed by clinical features or genetic testing,but all these mutations were detected in their offspring,except for the variant 6325C>T.We also found that a few young members of the family of probands(proband 1 and proband 2)have exhibited no manifestations of MFS so far,although they carry the same disease-causing mutation.Conclusions:We found three FBN1 mutations in three unrelated Chinese families with MFS by genome sequencing,and the relationship between genotypes and phenotypes in MFS patients needs further exploration.

Marfan Syndrome Complicated by Aortic Arch Aneurysm and Aortic Dissection: A Case Report from Congo

Context and Aim: Marfan syndrome is a transmissible genetic disease of the connective tissue that is rarely encountered in Congo and in sub-Saharan African countries. Its cardiovascular complications can be life frightening. The management of that disease is still limited in our country because of a lack of technical capacity in cardiovascular surgery. The aim of this clinical report is to show the interest of echocardiography and especially angioscanner as the main technique in the diagnosis of the severity of this disease, elaborate a literature review, but also to highlight the difficulties encountered in the management of that affection in our countries. Observation: The authors report the medical observation of a 48-year-old adult with a history of cataract of the left eye and a subluxation of the lens for which he underwent surgery in 2016, without any etiology being found. He is a smoker at a rate of 6 packs yearly. He consulted for progressively worsening dyspnea and constrictive mediosternal pain. The clinical examination revealed a moderate alteration of the general state, apyrexia, a blood pressure of 140/90 mmHg, a SPO2 of 97% in ambient air, a respiratory frequency of 32 cycles/min, signs of left ventricular insufficiency, a diastolic murmur of aortic insufficiency of intensity 4/6th, a long-limbed morphotype with a wingspan superior to the height and a kyphoscoliosis. Chest X-ray showed cardiomegaly with a cardiothoracic ratio of 58%, a highly dilated and uncoiled aorta, convexity of the left inferior arch, and venocapillary hypertension and a quiet alveolar-interstitial pulmonary oedema. The ECG was in sinus rhythm and showed a poor R-wave progression in anteroseptal leads. Echocardiography showed significant aortic root dilatation up to 72.6 mm and aortic regurgitation grade IV. Angioscanner showed a dissected aortic aneurysm and areas of emphysema located in the lungs. The medical treatment was palliative with beta blocker and angiotensin II receptor antagonists, diuretics and analgesics. The patient is awaiting surgery. Conclusion: Marfan syndrome is a genetic disease of the connective tissue that can manifest itself by cardiovascular, pulmonary, orthopedic, ophthalmological and cutaneous signs. Echocardiography and especially angioscanner are the tools of choice for the diagnosis and follow-up of this condition. Surgery is reserved for serious complications of this condition.

Marfan Syndrome with Systemic Lupus erythematosus

One of the autosomal dominant tissue disorders is Marfan syndrome that affects different organ systems.Mainly,Marfan syndrome causing abnormalities in the heart,blood vessels,eyes,bones,and joints.Most Often,features of Marfan syndrome are vision problems,defects in the large blood vessel-like aorta,tall and very thin,have long fingers and toes(arachnodactyly),and have an arm span exceeding the height of their body.Moreover,Other common features include a long and narrow face,crowded teeth,and scoliosis,or kyphosis.We presented a thirty-three years old female known case of Systemic Lupus erythematosus(SLE)and had Marfan syndrome,presented to the emergency department with complaints of headache and fever for two days.The patient denied any complaining of vomiting,blurred vision,dizziness.

Neonatal Marfan Syndrome: Improving the Bad Prognosis with a Strict Conservative Treatment with Carvedilol?

We report about a successful heart failure therapy with carvedilol in two children with neonatal Marfan syndrome (nMFS). As shown in Case 1, double valve replacement in an infant with neonatal Marfan syndrome is feasible but its benefit on long term is uncertain. Excluding our patient, 3 infants with nMFS from the literature died early after cardiac surgery. Our second case is a unique patient who survives nMFS despite diaphragmatic herniae, dilated neonatal cisterna magna and severe atrioventricular valve insufficiencies. Treated with 0.7 mg/kg/day Carvedilol since his seventh month of life, he never developed severe heart failure. However despite his good health status at the age of 9 years, a progressive aortic root dilatation and left conornary aneurysm are still waiting for surgical repair.

Application of next-generation sequencing to screen for pathogenic mutations in 123 unrelated Chinese patients with Marfan syndrome or a related disease

Marfan syndrome(MFS) is a systemic connective tissue disease principally affecting the ocular, skeletal and cardiovascular systems. This autosomal dominant disorder carries a prevalence of 1:3,000 to 1:5,000. This study aims to define the mutational spectrum of MFS related genes in Chinese patients and to establish genotype-phenotype correlations in MFS. Panel-based targeted next-generation sequencing was used to analyze the FBN1, TGFBR1 and TGFBR2 genes in 123 unrelated Chinese individuals with MFS or a related disease. Genotype-phenotype correlation analyses were performed in mutation-positive patients. The results showed that 97 cases/families(78.9%;97/123) harbor at least one(likely) pathogenic mutation, most of which were in FBN1;four patients had TGFBR1/2 mutations;and one patient harbored a SMAD3 mutation. Three patients had two FBN1 mutations, and all patients showed classical MFS phenotypes. Patients with a dominant negative-FBN1 mutation had a higher prevalence of ectopia lentis(EL). Patients carrying a haploinsufficiency-FBN1 mutation tended to have aortic dissection without EL. This study extends the spectrum of genetic backgrounds of MFS and enriches our knowledge of genotype-phenotype correlations.

Molecular analysis for diagnosis of Marfan syndrome and Marfan-associated disorders

Marfan syndrome is a systemic disorder of connective tissue, caused by mutations in the FBN1, TGFBR1 or TGFBR2 genes. This syndrome is characterized by involvement of three major systems, skeletal, ocular, and cardiovascular. The continuing improvements in molecular biology and increasing availability of molecular diagnosis in clinical practice allow recognition of Marfan syndrome in patients with incomplete phenotypes. Additionally, molecular analyses could also be used for preimplantation genetic diagnosis. The identification of a mutation allows for early diagnosis, prognosis, genetic counseling, preventive management of carriers and reassurance for unaffected relatives. The importance of knowing in advance the location of the putative family mutation is highlighted by its straightforward application to prenatal and postnatal screening.

FBN1 mutation in Chinese patients with Marfan syndrome and its gene diagnosis using haplotype linkage analysis

Objectives To analyze the FBN1 mutations in Chinese patients with Marfan syndrome (MFS) and to make a genetic diagnosis based on haplotype linkage analysis for MFS Methods Nine MFS families (17 patients) were analyzed with single strand conformation polymorphism (SSCP) and sequencing Four primers were designed for the flanking sequences of FBN1 gene and used for haplotype segregation analysis of MFS (B) Results SSCP band alteration was detected in the PCR products for exon 25 in MFS(A) Ⅱ∶1 Direct sequencing revealed a small 13 bp deletion; the deleted sequence is gccTc^Tgcaccca at bases 3243-3456 of the cDNA in exon 25 This mutation was novel MFS(B) families were analyzed using the haplotype linkage technique The data suggested that MFS(B) families were linked to the FBN1 gene The proband's daughter was an asymptomatic patient Conclusion The combination of mutation detection and chromosome haplotype analysis can provide better evidence for a genetic diagnosis of MFS

Missense mutations of the fibrillin-1 gene in two Chinese patients with severe Marfan syndrome

Objective To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene.Methods Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23 - 32,where the mutational hotspots for severe forms of Marfan syndrome are located.Results Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation.Conclusion Taking advantage of the clustering phenomenon of mutations in severe forms of Marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots,thus reducing the effort that would otherwise be much greater because of the size of the gene.

Clinical presentation and surgical treatment of scoliosis in Marfan syndrome

Marfan syndrome （MFS） as an autosomal dominant connective tissue disease is characterized by ocular, cardiovascular, and skeletal deformities including scoliosis. A group of 12 patients with Marfan syndrome associated with scoliosis were surgically treated at our hospital from January 1990 to January 2004.

Aneurysmal dilatation of the aortic sinuses of Valsalva -- beyond Marfan syndrome： a single centre experience and review of the literature

Aneurysmal dilatation of the aortic sinuses of Valsalva has been most extensively documented in the setting of aortopathies, particularly Marfan syndrome. On the other hand, there is limited data in the literature about congenital sinus of Valsalva aneurysms outside this context. For the purpose of this review, we carried out a literature search on aneurysmal dilatation of the sinuses of Valsalva in Marfan syndrome, and compared this with congenital sinus of Valsaiva aneurysms, also including data from a case series from our institution. In conclusion, there are differences in management of aortic dilatation in Marfan syndrome and congenital sinus of Valsalva aneurysms. Though less weil-recognised, congenital aneurysms are often associated with significant morbidity and mortality and timely intervention is necessary.

Evaluation of axial length/total corneal refractive power ratio as a potential marker for ocular diagnosis of Marfan’s syndrome in children

AIM:To investigate whether the axial length(AL)/total corneal refractive power(TCRP)ratio is a sensitive and simple factor that can be used for the early diagnosis of Marfan’s syndrome(MFS)in children.METHODS:The relationship between the AL/TCRP ratio and the diagnosis of MFS for 192 eyes in 97 children were evaluate.The biological characteristics,including age,sex,AL,and TCRP,were collected from medical records.Receiver operating characteristic(ROC)curve analysis was performed to investigate whether the AL/TCRP ratio effectively distinguishes MFS from other subjects.The Youden index was used to re-divide the whole population into two groups according to an AL/TCRP ratio of 0.59.RESULTS:Of 96 subjects(mean age 7.46±3.28 y)evaluated,56(110 eyes)had a definite diagnosis of MFS in childhood based on the revised Ghent criteria,41(82 eyes)with diagnosis of congenital ectopia lentis(EL)were included as a control group.AL was negatively correlated with TCRP,with a linear regression coefficient of-0.36(R2=0.08).A significant correlation was found between age and the AL/TCRP ratio(P=0.023).ROC curve analysis showed that the AL/TCRP ratio distinguished MFS from the other patients at a threshold of 0.59.MFS patients were present in 24/58(41.38%)patients with an AL/TCRP ratio of≤0.59 and in 34/39(87.18%)patients with an AL/TCRP ratio of>0.59.CONCLUSION:An AL/TCRP ratio of>0.59 is significantly associated with the risk of MFS.The AL/TCRP ratio should be measured as a promising marker for the prognosis of children MFS.Changes in the AL/TCRP ratio should be monitored over time.

A novel FBN1 missense mutation (p.C102Y) associated with ectopia lentis syndrome in a Chinese family

AIM: To characterize the disease-causing mutations in a Chinese family with ectopia lentis syndrome (ELS). METHODS: Patients and their family members were given complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA samples were extracted from the peripheral blood of the pedigree members and 100 healthy controls. Mutation screening was performed in the fibrillin -1 (FBN1) gene by bi -directional sequencing of the amplified products. The mutation was analyzed using two bioinformatics methods. RESULTS: A novel heterozygous c.305G>A mutation in exon 3 of FBN1 was detected. As a result of this change, a highly conserved cysteine residue was replaced by a tyrosine residue (p.C102Y). Another mutation was found in the same exon (c.303T>C), which did not change the amino acid sequence. Both mutations were discovered in each affected individual, but not in the unaffected family members, or in 100 ethnically matched controls. A bioinformatics analysis predicted that mutation p.C102Y would affect protein function. CONCLUSION: In the first epidermal growth factor-like module, we identified a novel FBN1 mutation (p.C102Y), which caused ELS in the family. Our study presented a unique phenotype, including some distinct ophthalmic findings, such as hypoplasia of the iris and anisometropia. Our results expanded the mutation spectrum of FBN1 and enriched the overall knowledge of genotype-phenotype correlations due to FBN1 mutations.

TGF-β signaling in vascular biology and dysfunction

Transforming growth factor （TGF）-β family members are multifunctional cytokines that elicit their effects on cells, including endothelial and mural cells, via specific type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. Knock-out mouse models for TGF-β family signaling pathway components have revealed their critical importance in proper yolk sac angiogenesis. Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular syndromes such as hereditary hemorrhagic telangiectasia, primary pulmonary hypertension and Marfan syndrome. In this review, we present recent advances in our under- standing of the role of TGF-β receptor signaling in vascular biology and disease, and discuss how this may be applied for therapy.