Recurrent and founder mutations in the Netherlands: Extensive clinical variability in Marfan syndrome patients with a single novel recurrent fibrillin-1 missense mutation.

Background/Methods. Marfan syndrome (MFS) is a heritable connective tissue disorder usually caused by a mutation in the fibrillin 1 (FBN1) gene. Typical characteristics of MFS that have been described include dolichostenomelia, ectopia lentis and aortic root dilatation. However, there is great clinical variability in the expression of the syndrome's manifestations, both between and within families. Here we discuss the clinical variability of MFS by describing a large fourgeneration Dutch family with MFS.Results. Nineteen individuals of one family with a single missense FBN1 mutation (c.7916A>G) were identified. The same mutation was found in one unrelated person. Clinical variability was extensive and not all mutation carriers fulfilled the diagnostic criteria for MFS. Some patients only expressed mild skeletal abnormalities, whereas aortic root dilation was present in eight patients, an acute type A aortic dissection was recorded in two other patients, and a mitral valve prolapse was present in eight patients. In some patients cardiac features were not present on initial screening, but did however develop over time.Conclusion. MFS is a clinically highly variable syndrome, which means a meticulous evaluation of suspected cases is crucial. Mutation carriers should be re-evaluated regularly as cardiovascular symptoms may develop over time. (Neth Heart J 2010;18:85-9.).

In-hospital mortality and three-year survival after repaired acute type A aortic dissection.

Background. The results of acute type A dissection (AAD) surgery in the Netherlands are largely unknown, as was recently stated in a report by the Health Council of the Netherlands. In order to gain more insight into the Dutch situation we investigated predictors of in-hospital mortality of surgically treated AAD patients and assessed threeyear survival.Methods. 104 consecutive patients undergoing surgery for AAD in a 16-year period (1990-2006) were evaluated. Preoperative and intraoperative variables were analysed to identify predictors of early mortality.Results. Preoperative malperfusion (limb ischaemia or mesenteric ischaemia) was present in 15.4%, shock in 18.3%, and 6.7% were operated under cardiac massage. Marfan syndrome was present in four patients and four patients had a bicuspid aortic valve. In-hospital mortality was 22.1%. Seven patients died intraoperatively; other causes of inhospital mortality were major brain damage in ten patients, multiple organ failure in three patients, low cardiac output in two patients and sudden cardiac death in one patient. Multivariate logistic regression revealed preoperative malperfusion (p=0.004) to be the only independent predictor of in-hospital mortality. Three-year survival was 68.8+/-4.7% (including hospital mortality). Hospital survivors had a three-year survival of 88.3+/-3.9%.Conclusion. In-hospital mortality of our patients (22.1%) is comparable with the results of larger case series published in the literature. Prognosis after successful surgical treatment is relatively good with a three-year survival of 88.3% in our series. (Neth Heart J 2009;17:226-31.).

The many faces of aggressive aortic pathology: Loeys-Dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a newly recognised disorder of connective tissue which shares overlapping features with Marfan syndrome (MFS) and the vascular type of Ehlers-Danlos syndrome, including aortic root dilatation and skin abnormalities. It is clinically classified into types 1 and 2. LDS type 1 can be recognised by craniofacial characteristics, e.g. hypertelorism, bifid uvula or cleft palate, whereas these are absent in LDS type 2. It is important to recognise LDS because its vascular pathology is aggressive. We describe nine LDS patients from four families, relate their features to published cases, and discuss important aspects of the diagnosis and management of LDS in order to make clinicians aware of this new syndrome. RESULTS: Characteristics found in the majority of these LDS patients were aortic root dilatation, cleft palate and/or a bifid/abnormal uvula. CONCLUSION: Because aortic dissection and rupture in LDS tend to occur at a young age or at aortic root diameters not considered at risk in MFS, and because the vascular pathology can be seen throughout the entire arterial tree, patients should be carefully followed up and aggressive surgical treatment is mandatory. Clinicians must therefore be aware of LDS as a cause of aggressive aortic pathology and that its distinguishing features can sometimes be easily recognised. (Neth Heart J 2008;16:299-304.).