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.

中文翻译：

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马凡综合征与 Loeys-Dietz 综合征 4 型的鉴别诊断：一种新型的 TGFB2 染色体缺失

马凡综合征 (MFS) 和 Loeys-Dietz 综合征 4 型 (LDS4) 是两种遗传性结缔组织疾病。MFS 显示晶状体异位是一个显着的特征性特征，而胸主动脉扩张、动脉瘤、夹层和全身性特征是与 LDS4 重叠的表现。LDS4 的特点是存在眼距过宽、腭裂和/或悬雍垂双歧，其他动脉可能出现扩张或动脉瘤。临床表现发病年龄的可变性使临床诊断更加困难。在这项研究中，我们根据该综合征的典型临床表现，报告了一名 33 岁在我中心诊断的马凡综合征患者的病例。38 岁时，左侧髂总动脉出现扩张和髂动脉迂曲提示存在 LDS4。下一代测序 (NGS) 分析，随后是 Array-CGH，允许检测到包括整个 TGFB2 基因在内的新染色体缺失，不仅证实了 LDS4 的临床怀疑，而且证实了与单倍体不足机制相关的临床表型，即，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。这个标志性的案例证实了我们在这两种病理的鉴别诊断中必须非常小心，尤其是在 40 岁之前，尤其是在怀疑受 MFS 影响的年轻受试者中，我们必须验证诊断，扩展基因分析，必要时，寻找染色体改变。最近，据报道，一名 LDS4 患者出现晶状体异位症，证实了这两种综合征之间的紧密重叠。非常需要对表征和重叠两种病理的临床参数进行准确修订。