Centre National de Référence pour le syndrome de Marfan et apparentés, Hôpital Bichat, Paris 75018, France.
Heart. 2011 Aug;97(15):1206-14. doi: 10.1136/hrt.2010.212100.
Marfan syndrome has changed over the last few years: new diagnostic criteria have been proposed, new clinical entities recognised and life expectancy increased. The role of fibrillin 1, which was initially thought to be mainly structural, has been shown to also be functional. The altered transforming growth factor β pathway is better understood, the importance of epigenetic factors has been demonstrated and recent data suggest that many of the observations made in Marfan syndrome can actually be made in thoracic aortic aneurysm from diverse aetiologies. Besides transforming growth factor β, the role of metalloproteinase, the fibrinolytic/coagulation system, is being suggested in the progression of the disease. A relationship between the type of fibrillin 1 (FBN1) gene mutation and the mechanism for the disease (haplo-insufficiency vs negative dominance), as well as some genotype/phenotype correlations, has been observed, although the main challenge of recognising gene modifiers has yet to explain tremendous variability despite similar mutation. This progress has led to new hopes for tomorrow's therapies, some of which are being tested in clinics, whereas others are still in the field of animal models. Here we review some of the new data obtained in the understanding of the pathophysiology and genetics of this disease.
提出了新的诊断标准，认识到了新的临床实体，并且预期寿命延长了。最初认为主要起结构作用的原纤维蛋白 1 的作用也被证明具有功能性。对改变的转化生长因子 β 途径有了更好的理解，已经证明了表观遗传因素的重要性，最近的数据表明，马凡综合征中的许多观察结果实际上也可以在不同病因的胸主动脉瘤中观察到。除了转化生长因子 β 外，金属蛋白酶、纤维蛋白溶解/凝血系统的作用也被认为与疾病的进展有关。已经观察到原纤维蛋白 1 (FBN1) 基因突变的类型与疾病的机制（单倍体不足与负显性）之间存在关系，以及一些基因型/表型相关性，尽管识别基因修饰剂的主要挑战仍然是解释尽管存在相似的突变，但仍存在巨大的可变性。这一进展为明天的治疗带来了新的希望，其中一些正在临床试验中进行测试，而另一些仍处于动物模型领域。在这里，我们回顾了在理解这种疾病的病理生理学和遗传学方面获得的一些新数据。
