PDF(Pubmed)
Abstract：
Marfan syndrome (MFS) and Loeys-Dietz syndrome type 4 (LDS4) are two hereditary connective tissue disorders. MFS displays ectopia lentis as a distinguishing, characterising feature, and thoracic aortic ectasia, aneurysm, dissection, and systemic features as manifestations overlapping with LDS4. LDS4 is characterised by the presence of hypertelorism, cleft palate and/or bifid uvula, with possible ectasia or aneurysms in other arteries. The variable age of onset of clinical manifestations makes clinical diagnosis more difficult. In this study, we report the case of a patient with Marfan syndrome diagnosed at our centre at the age of 33 on the basis of typical clinical manifestations of this syndrome. At the age of 38, the appearance of ectasia of the left common iliac artery and tortuosity of the iliac arteries suggested the presence of LDS4. Next Generation Sequencing (NGS) analysis, followed by Array-CGH, allowed the detection of a novel chromosomal deletion including the entire TGFB2 gene, confirming not only the clinical suspicion of LDS4, but also the clinical phenotype associated with the haploinsufficiency mechanism, which is, in turn, associated with the deletion of the entire gene. The same mutation was detected in the two young sons. This emblematic case confirms that we must be very careful in the differential diagnosis of these two pathologies, especially before the age of 40, and that, in young subjects suspected to be affected by MFS in particular, we must verify the diagnosis, extending genetic analysis, when necessary, to the search for chromosomal alterations. Recently, ectopia lentis has been reported in a patient with LDS4, confirming the tight overlap between the two syndromes. An accurate revision of the clinical parameters both characterising and overlapping the two pathologies is highly desirable.
摘要：
Marfan综合征（MFS）和Loeys-Dietz综合征4型（LDS4）是两种遗传性结缔组织疾病。MFS显示外翻作为一种区别，表征特征，和胸主动脉扩张，动脉瘤,解剖,和系统特征表现为与LDS4重叠。LDS4的特点是存在超端粒，腭裂和/或悬垂双裂，其他动脉可能有扩张或动脉瘤。临床表现的发病年龄可变，使临床诊断更加困难。在这项研究中,我们报道了一例在本中心诊断为马凡氏综合征的患者,其年龄为33岁,根据该综合征的典型临床表现.38岁时，左髂总动脉扩张和髂动脉弯曲的出现表明存在LDS4。下一代测序（NGS）分析，其次是Array-CGH，允许检测包括整个TGFB2基因的新染色体缺失，不仅证实了LDS4的临床怀疑，而且证实了与单倍体功能不全机制相关的临床表型，也就是说，反过来,与整个基因的缺失有关.在两个年幼的儿子中检测到相同的突变。这个具有代表性的病例证实了我们在鉴别诊断这两种疾病时必须非常小心，尤其是在40岁之前，特别是在怀疑受MFS影响的年轻受试者中，我们必须验证诊断，扩展遗传分析，必要时,寻找染色体改变。最近,据报道，LDS4患者出现外翻，证实了两种综合征之间的紧密重叠。非常需要精确修正表征和重叠两种病理的临床参数。
