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Eur J Clin Invest 2010 ABSTRACT: Background  Fetuin-A is a glycoprotein that inhibits extraosseous and vascular calcification. Its serum level is lower in patients with atherosclerosis compared with healthy controls, but its role is unknown in aneurysmal diseases. The aim of our study was to investigate the association of serum fetuin-A levels with aortic aneurysms of different aetiology: Marfan syndrome and atherosclerosis. Material and methods  In a single centre cross-sectional observational study, 105 patients (30 with atherosclerotic aortic aneurysm, 15 with Marfan syndrome, 30 with peripheral arterial disease and 30 healthy controls) were examined; sera were analysed for fetuin-A, standard markers of possible inflammation, lipid profile, kidney and hepatic disease and diabetes. Systemic atherosclerosis was assessed by carotid intima-media thickness (IMT) measurement and arterial calcification score of cardiac valves, carotids, aorta and femoral arteries determined by ultrasound. Results  Serum fetuin-A levels (median and IQR) were significantly lower in the atherosclerotic aneurysm cohort than in patients with Marfan syndrome: 708 μg mL(-1)  (612-780) and 756 μg mL(-1)  (708-816), respectively, (P = 0·0428). Fetuin-A levels were 754 μg mL(-1)  (713-777) in the control group and 654 μg mL(-1)  (600-756) in patients with peripheral arterial disease. Mean and maximum IMT, ACS values and homocysteine levels were significantly higher in patients with atherosclerosis: P < 0·0001, P < 0·0001, P < 0·0001 and P = 0·0034, respectively. There was no significant difference between aneurysm groups analysing the results of lipid profile and acute-phase markers. Conclusions  The significantly lower serum level of fetuin-A in the atherosclerotic aneurysm group supports the protective role of fetuin-A in the evolution of arterial calcification. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation

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Fiatalkorúak Marfan-betegségének ismertetése kapcsán utaltunk a m. dilatator pupilláé gyakori veleszületett hiányára, amelynek következtében az ilyen betegek pupilláját a szokásos atropin szemcseppel nem lehet kitágítani. Említettük továbbá, hogy a veleszületett izom-defectus meglehetősen ritka anomália, még leggyakoribb a m. pectoralis maior hiánya, amely része a Poland-féle symptoma-complexumnak. A következőkben saját észlelés alapján ismertetjük a Poland-syndromát, amelyet egyik Marfan-betegünkön figyeltünk meg.

Link: http://www.ncbi.nlm.nih.gov/pubmed/4312055

Absztrakt

A Marfan-syndroma legjellegzetesebb tünetei 1. a csontvázra, 2. a szemre, és 3. a cardiovascularis systemára localisálódnak. Előző közleményünkben vázoltuk a fiatalkorú Marfan-betegek rendszeres cardiológiai ellenőrzésének szükségességét, minthogy az ilyen betegek prognózisát quo ad vitám a szív- és nagyérelváltozások (aorta-elongatio, dilatatio, aneurysma) határozzák meg. A korai kórismézéshez hatékony szűrővizsgálati módszerek szükségesek. Ilyenek a lencse-luxatio és -subluxatio vizsgálata, illetve a Varga-féle index kiszámítása. Van azonban ezeknél jóval egyszerűbb módszer: a Steinberg-féle hüvelykujj-tünet, amelyet az alábbiakban kívánunk Magyarországon elsőként ismertetni, s gyakorlati használhatóságához reflexiót fűzni.

Link: http://www.ncbi.nlm.nih.gov/pubmed/5364767

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Az egyszerű megtekintés ma is fontos része az orvosi vizsgálatnak, mert az esetleges congenitalis asymmetria (hemihypertrophia, hemiatrophia), illetve a testmagasság és testsúly enormis volta így kerül felismerésre. Bár a Marfan-betegség legjellegzetesebb tünete a végtagok hosszú és keskeny volta („dolichostenomelia", Marfan, 1896), illetve a kéz- és lábujjak póklábhoz hasonlósága ("pieds d'aragne", Marfan és "arachnodaktylia", Achard, 1912), mégis főleg a betegek szokatlan testmagassága az, ami helyes irányba tereli a figyelmet. A betegség külső tüneteinek a lényege tehát a feltűnő soványság és szokatlan testmagasság, amelyek inspectiója alkalmával - főleg az osteothorax gyakori deformáltsága miatt - még az a benyomásunk is támad, hogy nem csupán magas és sovány, de egyszersmind gyenge, törékeny alkatú beteggel van dolgunk.

Link: http://www.ncbi.nlm.nih.gov/pubmed/5372817

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A Marfan-syndroma nem egyszerű csont-dystrophia, hanem az egész szervezet mélyreható megbetegedése. Légzőszervi vonatkozásai még alig ismertek. A következőkben 14 éves kisleány veleszületett tüdőrendellenességét ismertetjük. Ilyen légzőszervi manifestatiót eddig nem írtak le.

Link: http://www.ncbi.nlm.nih.gov/pubmed/5164951

Absztrakt

Marfan-syndroma alatt ma a szervezet mélyreható megbetegedését értjük, melynek lényegét a dolichostenomelia vagy arachnodactylia synonyma nem fejezi már ki. Kiderült idővel ugyanis, hogy nem egyszerű csont-dystrophiáról van szó, hanem más szervrendszerek egyidejű érintettsége is lehetséges. E testileg-lelkileg astheniás betegek boldogulását, munkabírását általában a látásromlás foka, s prognózisukat quo ad vitám cardiovascularis rendszerük állapota határozza meg. Ezért is tartozik az ilyen betegek ellátása a cardiovascularis gondozás profiljába. Ismertetendő betegünk sorsa azt bizonyítja, hogy az aorta falának kitágulása és megrepedése gyermekkorban is bekövetkezhet.

Link: http://www.ncbi.nlm.nih.gov/pubmed/5137743

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Ma már nem fogadható el azon nézet, amely szerint a Marfan-syndroma kizárólag a mesodermalis eredetű szervek vele született dystrophiája. A betegség jól ismert csontrendszeri, szemészeti és cardiovascularis componensein kívül ugyanis újabban a tüdők, a gyomorbélhuzam, sőt az idegrendszer részvételéről is kétségtelen bizonyítékaink vannak. Nyilvánvaló ma már, hogy Marfan-syndromában a mesoderma állandó részvétele mellett ritkábban az entoderma, illetve az ectoderma fejlődési zavara is szerepet játszhat. Vannak, akik a Marfan-syndromát a mucopolysaccharidosisok közé sorolják. Becslésünk szerint már 1000 felett van a Marfan-syndromás publicált esetek száma, de a dermatológiai vonatkozású megfigyelések leírása rendkívül ritka. A Marfan-syndroma kapcsán kimutatott dermatológiai elváltozások közül a striae atrophicae a legjelentősebbek és váltották ki eddig a legnagyobb érdeklődést. A következőkben 4 Marfan-syndromás betegünkről, illetve bőr csíkjaikról számolunk be. Nagy Marfan-syndromás anyagunkban megfigyelt dermatológiai tüneteket összefoglalólag más helyen ismertetjük.

Link: http://www.ncbi.nlm.nih.gov/pubmed/4741367

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A Marfan-syndroma iránt egyre fokozódik a kutatók és a legkülönbözőbb orvosi szakok érdeklődése. Magyarázhatjuk ezt - egyebek között - a humángenetikai kórképek általános előtérbe kerülésével, valamint a Marfan-syndromás betegek egyre hatékonyabb szívsebészeti kezelésével is. Ezáltal e betegség lehető legkoraibb felismerésének a gyakorlati jelentősége csak fokozódott. Ennek érdekében még napjainkban is újabb és újabb, még megfelelőbb szűrővizsgálati módszerek után kutatnak. Ilyen célzattal írta le 1970-ben Walker és Murdoch az un. "csukló-jel"-et. Ennek használhatóságára vonatkozó tapasztalatainkról számolunk be a következőkben úgy, hogy egyben párhuzamot is vonunk a csukló-jel és a Steinberg-tünet között.

Link: http://www.ncbi.nlm.nih.gov/pubmed/1244598

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Az elmúlt 17 év (1982-98) során 72 esetben elvégzett aorta-gyök rekonstrukcióról (Bentall 66, Cabrol 6) számolnak be. A műtétet indokló kórkép 39%-ban "A" típusú aorta dissectio, 40,3%-ban aorta vitiumhoz társuló aorta ascendens aneurysma, 13,8%-ban aorto-annulectasia, 5,5%-ban korábbi szívműtétet követően kialakult és rupturált aorta aneurysma és egy esetben aorta billentyű endocarditis volt. A műtétre került betegek 29%-a szenvedett Marfan szindrómában. A Bentall, illetve Cabrol műtét valójában csak 1993-tól vált rutin bea- vatkozássá. Az utolsó 5 és fél évre esett a műtétek 70%-a. Az 1982-92 között eltelt "tanuló" évtized és az 1993 óta eltelt időszak élesen elkülönül a műtéti eredményesség vonatkozásában is. Az első időszak elektív műtéti halálozása 47%-ról 2,9%-ra csökkent az utóbbi években. Az akut beavatkozások esetében látványos javulás nem volt tapasztalható: 50% vs. 43,8%. 50 betegnél átlagosan 57,326,78 (1-185) hónap utánkövetés ered- ményeiről számolnak be. A kontroll echo vizsgálatok a posztoperatív ejekciós frakciókat szignifikánsan jobbnak (p<0,05), a bal kamra systolés (p<0,01) és diastolés átmérőjét (p<0,01) pedig szignifikánsan kisebbnek találta a műtét előtt mértekkel összehasonlítva. Szerzők végkövetkeztetései: 1. Megfelelő műtéti technika mellett az elektív Bentall és Cabrol műtét alacsony rizikójú beavatkozás, 2. Megfelelő műtéti technika önerőből történő elsajátítása időt igényel (learning curve), 3. A sikeresen operáltak tartósan panaszmentesen, jó functionális állapotban maradnak

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Mutations in the human fibrillin 1 gene (FBN1) cause the Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Knowledge about FBN1 mutations is important for early diagnosis, management, and genetic counseling. However, mutation detection in FBN1 is a challenge because the gene is very large in size ( approximately 200 kb) and the approximately 350 mutations detected so far are scattered over 65 exons. Conventional methods for large-scale detection of mutations are expensive, technically demanding, or time consuming. Recently, a high-capacity low-cost mutation detection method was introduced based on denaturing high-performance liquid chromatography (DHPLC). To assess the sensitivity and specificity of this method, we blindly screened 64 DNA samples of known FBN1 genotype exon-by-exon using exon-specific DHPLC conditions. Analysis of 682 PCR amplicons correctly identified 62 out of 64 known sequence variants. In three MFS patients of unknown FBN1 genotype, we detected two mutations and eight polymorphisms. Overall, 20 mutations and two polymorphisms are described here for the first time. Our results demonstrate 1) that DHPLC is a highly sensitive (89-99%, P = 0.05) method for FBN1 mutation detection; but 2) that chromatograms with moderate and weak pattern abnormalities also show false positive signals (in all 45-59%, P = 0.05); 3) that the difference in the chromatograms of heterozygous and homozygous amplicons is mostly independent of the type of sequence change; and 4) that DHPLC column conditions, additional base changes, and the amounts of injected PCR products influence significantly the shape of chromatograms. A strategy for FBN1 mutation screening is discussed. Copyright 2002 Wiley-Liss, Inc.

Link: http://www.ncbi.nlm.nih.gov/pubmed/11933199

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OBJECTIVES: Marfan syndrome (MFS) is an autosomal dominant inherited connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene with variable clinical manifestations in the cardiovascular, musculoskeletal and ocular systems. METHODS: Data of moleculor genetic analysis and a catalogue of clinical manifestations including aortic elastic parameters were mined in order to (i) assess aortic abnormality before and during medical treatment, and to (ii) identify novel correlations between the genotype and phenotype of the disease using hierarchical cluster analysis and logistic regression analysis. A score measure describing the similarity between a patient's clinical symptoms and a characteristic phenotype class was introduced. RESULTS: A probabilistic model for monitoring the loss of aortic elasticity was built on merely aortic parameters of 34 patients with classic MFS and 43 control subjects showing a sensitivity of 82% and a specificity of 96%. The clinical phenotypes of 100 individuals with classical or suspected MFS were clustered yielding four different phenotypic expressions. The highest correlation was found between FBN1 missense mutations, which manifested as ectopia lentis, skeletal major and skin minor criteria, and two out of four clustered phenotypes. The probability of the presence of a missense mutation in both phenotype classes is approximately 70%. CONCLUSIONS: Monitoring of aortic elastic properties during medical treatment may serve as additional criterion to indicate elective surgical interventions. Genotype-phenotype correlation may contribute to anticipate the clinical consequences of specific FBN1 mutations more comprehensively and may be helpful to identify MFS patients at risk at on early stage of disease.

Link: http://www.ncbi.nlm.nih.gov/pubmed/16342915

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BACKGROUND: In patients with Marfan syndrome, progressive aortic dilation implicates a still-unpredictable risk of life-threatening aortic dissection and rupture. We sought to quantify aortic wall dysfunction noninvasively, determine the diagnostic power of various aortic parameters, and establish a diagnostic model for the early detection of aortic abnormalities associated with Marfan syndrome. METHODS: In 19 patients with Marfan syndrome (age, 17.7 +/- 9.5 years) and 19 age- and sex-matched healthy control subjects, computerized ascending and abdominal aortic wall contour analysis with continuous determination of aortic diameters was performed out of transthoracic M-mode echocardiographic tracings. After simultaneous oscillometric blood pressure measurement, aortic elastic properties were determined automatically. RESULTS: The following ascending aortic elastic parameters showed statistically significant differences between the Marfan group and the control group: (1) decreased aortic distensibility ( P < .001), (2) increased wall stiffness index ( P < .01), (3) decreased systolic diameter increase ( P < .01), and (4) decreased maximum systolic area increase ( P < .001). The diagnostic power of all investigated parameters was tested by single logistic regression models. A multiple logistic regression model including solely aortic parameters yielded a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: In young patients with Marfan syndrome, a computerized image-analyzing technique revealed decreased aortic elastic properties expressed by parameters showing high diagnostic power. A multiple logistic regression model including merely aortic parameters can serve as useful predictor for Marfan syndrome.

Link: http://www.ncbi.nlm.nih.gov/pubmed/15821637

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Mutations in the human FBN1 gene are known to be associated with the Marfan syndrome, an autosomal dominant inherited multi-systemic connective tissue disorder. However, in the absence of solid genotype-phenotype correlations, the identification of an FBN1 mutation has only little prognostic value. We propose a bioinformatics framework for the mutated FBN1 gene which comprises the collection, management, and analysis of mutation data identified by molecular genetic analysis (DHPLC) and data of the clinical phenotype. To query our database at different levels of information, a relational data model, describing mutational events at the cDNA and protein levels, and the disease's phenotypic expression from two alternative views, was implemented. For database similarity requests, a query model which uses a distance measure based on log-likelihood weights for each clinical manifestation, was introduced. A data mining strategy for discovering diagnostic markers, classification and clustering of phenotypic expressions was provided which enabled us to confirm some known and to identify some new genotype-phenotype correlations.

Link: http://www.ncbi.nlm.nih.gov/pubmed/16061422

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Very recently, heterozygous mutations in the genes encoding transforming growth factor beta receptors I (TGFBR1) and II (TGFBR2) have been reported in Loeys-Dietz aortic aneurysm syndrome (LDS). In addition, dominant TGFBR2 mutations have been identified in Marfan syndrome type 2 (MFS2) and familial thoracic aortic aneurysms and dissections (TAAD). In the past, mutations of these genes were associated with atherosclerosis and several human cancers. Here, we report a total of nine novel and one known heterozygous sequence variants in the TGFBR1 and TGFBR2 genes in nine of 70 unrelated individuals with MFS-like phenotypes who previously tested negative for mutations in the gene encoding the extracellular matrix protein fibrillin-1 (FBN1). To assess the pathogenic impact of these sequence variants, in silico analyses were performed by the PolyPhen, SIFT, and Fold-X algorithms and by means of a 3D homology model of the TGFBR2 kinase domain. Our results showed that in all but one of the patients the pathogenic effect of at least one sequence variant is highly probable (c.722C > T, c.799A > C, and c.1460G > A in TGFBR1 and c.773T > G, c.1106G > T, c.1159G > A, c.1181G > A, and c.1561T > C in TGFBR2). These deleterious alleles occurred de novo or segregated with the disease in the families, indicating a causative association between the sequence variants and clinical phenotypes. Since TGFBR2 mutations found in patients with MFS-related disorders cannot be distinguished from heterozygous TGFBR2 mutations reported in tumor samples, we emphasize the importance of segregation analysis in affected families. In order to be able to find the mutation that is indeed responsible for a MFS-related phenotype, we also propose that genetic testing for sequence alterations in TGFBR1 and TGFBR2 should be complemented by mutation screening of the FBN1 gene.

Link: http://www.ncbi.nlm.nih.gov/pubmed/16791849

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OBJECTIVE: Aortic complications determine the life expectancy of most patients with Marfan syndrome. To find out whether there is heterogenous aortic involvement among patients and, if there is, to characterize aortic patterns and response to long-term beta-blocker therapy, we investigated aortic elastic properties before and during beta-blocker treatment. METHODS: In 46 patients with Marfan syndrome (age, 17.4 +/- 11.1 years) and 46 healthy control subjects, ascending and descending aortic elastic parameters were determined noninvasively before and after 39 +/- 16 months of beta-blocker treatment with atenolol. RESULTS: Aortic diameters and distensibility distinguished Marfan patients and controls with a sensitivity of 85% and a specificity of 87%. Cluster analysis revealed 4 patterns of aortic phenotypic expression: (1) reduced ascending aortic elasticity (46% of patients), (2) diminished ascending and descending aortic elasticity (17%), (3) minimal alterations of ascending and descending aortic elasticity (20%), and (4) reduced descending aortic elasticity (17%). During follow-up, aortic elastic properties improved in 21 (70%) of 30 patients and deteriorated in 9 (30%) irrespective of beta-blocker dosage. Improvement was observed in 100% of patients (n = 7; age, 5.3 +/- 4.2 years) with end-diastolic aortic root diameters between 20 and 30 mm and in 61% of patients (14/23; age, 20.5 +/- 10.0 years) with root diameters between 30 and 52 mm. CONCLUSIONS: Aortic elastic parameters distinguish between patients with Marfan syndrome and healthy controls and show the pattern of regional aortic involvement. Improvement or deterioration during follow-up can influence therapeutic decisions to prevent aortic dissection and rupture. Young age, small root diameter, and high distensibility are favorable prognostic factors.

Link: http://www.ncbi.nlm.nih.gov/pubmed/17000292

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Mutations in the FBN1 gene are the major cause of Marfan syndrome (MFS), an autosomal dominant connective tissue disorder, which displays variable manifestations in the cardiovascular, ocular, and skeletal systems. Current molecular genetic testing of FBN1 may miss mutations in the promoter region or in other noncoding sequences as well as partial or complete gene deletions and duplications. In this study, we tested for copy number variations by successively applying multiplex ligation-dependent probe amplification (MLPA) and the Affymetrix Human Mapping 500 K Array Set, which contains probes for approximately 500,000 single-nucleotide polymorphisms (SNPs) across the genome. By analyzing genomic DNA of 101 unrelated individuals with MFS or related phenotypes in whom standard genetic testing detected no mutation, we identified FBN1 deletions in two patients with MFS. Our high-resolution approach narrowed down the deletion breakpoints. Subsequent sequencing of the junctional fragments revealed the deletion sizes of 26,887 and 302,580 bp, respectively. Surprisingly, both deletions affect the putative regulatory and promoter region of the FBN1 gene, strongly indicating that they abolish transcription of the deleted allele. This expectation of complete loss of function of one allele, i.e. true haploinsufficiency, was confirmed by transcript analyses. Our findings not only emphasize the importance of screening for large genomic rearrangements in comprehensive genetic testing of FBN1 but, importantly, also extend the molecular etiology of MFS by providing hitherto unreported evidence that true haploinsufficiency is sufficient to cause MFS.

Link: http://www.ncbi.nlm.nih.gov/pubmed/17492313

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Marfan-szindróma alatt a szervezet egészét érintő, autoszomális domináns módon öröklődő kötőszöveti elváltozást értünk, amely elsősorban a csontok, az ízületek, a szem, a szív- és érrendszer rendellenességét okozza, de a bőr, a tüdő, a vázizomzat valamint a központi idegrendszer érintettségével is járhat. Generalizált betegség lévén a klinikai kép igen változatos lehet, a tünetek megjelenhetnek enyhe és súlyos formában is. A betegség prevalenciája 1/10 000, nemtől és etnikumtól függetlenül, tehát jelenleg Magyarországon hozzávetőlegesen ezer Marfan-szindrómás beteg él.

Link: http://www.marfan.hu/doctors/diagnosis.php#family_doc

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Aortic root dilatation is present by the age of five years in approximately 35% of patients suffering from Marfan syndrome. However, children rarely undergo surgery for aortic aneurysm and aortic regurgitation during their first decade of life. A nine-year-old boy, who presented with severe aortic regurgitation associated with a 76.8 mm aneurysm of the ascending aorta, underwent a Bentall procedure. Since the aortic annulus was markedly dilated and the cusps were structurally abnormal, the aortic valve was not spared.

Link: http://www.ncbi.nlm.nih.gov/pubmed/19455899

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BACKGROUND: Marfan syndrome (MFS) is a heritable disorder of connective tissue, affecting principally skeletal, ocular, and cardiovascular systems. The most life-threatening manifestations are aortic aneurysm and dissection. We investigated changes in the proteome of aortic media in patients with and without MFS to gain insight into molecular mechanisms leading to aortic dilatation. METHODS AND RESULTS: Aortic samples were collected from 46 patients. Twenty-two patients suffered from MFS, 9 patients had bicuspid aortic valve, and 15 patients without connective tissue disorder served as controls. Aortic media was isolated and its proteome was analyzed in 12 patients with the use of 2-dimensional difference gel electrophoresis and mass spectrometry. We found higher amounts of filamin A C-terminal fragment, calponin 1, vinculin, microfibril-associated glycoprotein 4, and myosin-10 heavy chain in aortic media of MFS aneurysm samples than in controls. Regulation of filamin A C-terminal fragmentation was validated in all patient samples by immunoblotting. Cleavage of filamin A and the calpain substrate spectrin was increased in the MFS and bicuspid aortic valve groups. Extent of cleavage correlated positively with calpain 2 expression and negatively with the expression of its endogenous inhibitor calpastatin. CONCLUSIONS: Our observation demonstrates for the first time upregulation of the C-terminal fragment of filamin A in dilated aortic media of MFS and bicuspid aortic valve patients. In addition, our results present evidence that the cleavage of filamin A is highly likely the result of the protease calpain. Increased calpain activity might explain, at least in part, histological alterations in dilated aorta.

Link: http://www.ncbi.nlm.nih.gov/pubmed/19720936

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We improved, evaluated, and used Sanger sequencing for quantification of single nucleotide polymorphism (SNP) variants in transcripts and gDNA samples. This improved assay resulted in highly reproducible relative allele frequencies (e.g., for a heterozygous gDNA 50.0+/-1.4%, and for a missense mutation-bearing transcript 46.9+/-3.7%) with a lower detection limit of 3-9%. It provided excellent accuracy and linear correlation between expected and observed relative allele frequencies. This sequencing assay, which can also be used for the quantification of copy number variations (CNVs), methylations, mosaicisms, and DNA pools, enabled us to analyze transcripts of the FBN1 gene in fibroblasts and blood samples of patients with suspected Marfan syndrome not only qualitatively but also quantitatively. We report a total of 18 novel and 19 known FBN1 sequence variants leading to a premature termination codon (PTC), 26 of which we analyzed by quantitative sequencing both at gDNA and cDNA levels. The relative amounts of PTC-containing FBN1 transcripts in fresh and PAXgene-stabilized blood samples were significantly higher (33.0+/-3.9% to 80.0+/-7.2%) than those detected in affected fibroblasts with inhibition of nonsense-mediated mRNA decay (NMD) (11.0+/-2.1% to 25.0+/-1.8%), whereas in fibroblasts without NMD inhibition no mutant alleles could be detected. These results provide evidence for incomplete NMD in leukocytes and have particular importance for RNA-based analyses not only in FBN1 but also in other genes.

Link: http://www.ncbi.nlm.nih.gov/pubmed/19618372

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A Marfan-szindróma a szervezet kötőszöveti állományát érintő öröklődő betegség, amely Magyarországon hozzávetőleg 2–3000 személyt érint. A betegség manifesztációi multiszisztémásak, ezért a kórismézés sokszor nehézségekbe ütközik. Az „Országos Marfan Regiszter” jelenleg közel 250 Marfan-szindrómában szenvedő beteg adatait tartalmazza, s ez a szám dinamikusan növekszik. Célok: A Marfan-szindrómás magyar személyek biológiai mintáinak, klinikai adatainak és életmódfelmérőinek összegyűjtése. Módszerek: A szelekció során olyan betegekre esett a választás, akiknél a cardiovascularis és a szisztémás érintettség, illetve a családi kórelőzmény alapján az átdolgozott Gent-nozológia értelmében egyértelműen megállapítható a Marfan-szindróma fennállása. Eredmények: Az adatbázis alapján 102 Marfan-szindrómában szenvedő személyt tartalmaz a biobank, amely 55 személy cDNS-mintáját, 102 személy genomi DNS- és szérummintáját foglalja magába. A biológiai minták mellett minden személyről nemzetközileg validált fi zikai aktivitási, táplálkozási és pszichológiai kérdőívek alapján gyűjtött adatot is tartalmaz a biobank. Következtetések: A Marfan Biobank genetikai, génexpressziós és fehérjeszintű kutatások gyors megterve zését teszi lehetővé. A biobank hozzájárul a kórkép alaposabb megismeréséhez és a hazai betegek ellátásához egyaránt.

Link: http://www.akademiai.com/content/cr4xk7326552p710/fulltext.pdf

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Abstract The starting point, in Marfan syndrome (MFS) appears to be the mutation of fi brillin-1 gene whose deconstructed protein product cannot bind transforming growth factor beta (TGF-b), leading to an increased TGF-b tissue level. The aim of this review is to review the already known features of the cellular signal transduction downstream to TGF-b and its impact onthe tissue homeostasis of microfibrils, and elastic fi bers. We also investigate current data onthe extracellular regulation of TGF-b level including mechanotransduction and the feedback cycles of integrin-dependent and independent activation of the latent TGF-b complex. Togetherthese factors, by the destruction of the connective tissue fi bers, may play an important role inthe development of the diverse cardiac and extracardiac manifestations of MFS and many of them could be a target of conservative treatment. We present currently investigated drugs for thetreatment of the syndrome, and explore possible avenues of research into pathogenesis of MFS in order to improve understanding of the disease.

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Érvényesül-e az elvárható orvosi odafigyelés a Marfan szindrómásokkal kapcsolatban, avagy felismerjük-e egyáltalán a Marfan-szindrómát? Az itt bemutatott eset azt szemlélteti, hogy ezen a téren sok még a tennivaló. Az aortát érintő szövődmények korai felderítése életmentő lehet.

Absztrakt

Background According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. Methods A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-β (TGF-β) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and −9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. Results Among patients with aortic dissection, TGF-β serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2α = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. Conclusions We found three easily measurable parameters (striae atrophicae, TGF-β serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.

Link: http://www.biomedcentral.com/1471-2261/14/47