Erhart Philipp, Körfer Daniel, Dihlmann Susanne, Qiao Jia-Lu, Hausser Ingrid, Ringleb Peter, Männer Jörg, Dikow Nicola, Schaaf Christian P, Grond-Ginsbach Caspar, Böckler Dittmar
Department of Vascular and Endovascular Surgery, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Institute of Pathology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
J Clin Med. 2022 Jun 7;11(12):3264. doi: 10.3390/jcm11123264.
Although patients with multiple arterial dissections in distinct arterial regions rarely present with known connective tissue syndromes, we hypothesized that mild connective tissue abnormalities are common findings in these patients.
From a consecutive register of 322 patients with cervical artery dissection (CeAD), we identified and analyzed 4 patients with a history of additional dissections in other vascular beds. In three patients, dermal connective tissue was examined by electron microscopy. DNA from all four patients was studied by whole-exome sequencing and copy number variation (CNV) analysis.
The collagen fibers of dermal biopsies were pathologic in all three analyzed patients. One patient carried a CNV disrupting the and genes (vascular or hypermobility type of Ehlers-Danlos syndrome), and another patient a CNV in (familial thoracic aortic aneurysms and dissections). The third patient carried a missense substitution in .
Three patients showed morphologic alterations of the dermal connective tissue, and two patients carried pathogenic variants in genes associated with arterial connective tissue dysfunction. The findings suggest that genetic testing should be recommended after recurrent arterial dissections, independently of apparent phenotypical signs of connective tissue disorders.
尽管在不同动脉区域发生多处动脉夹层的患者很少表现出已知的结缔组织综合征，但我们推测轻度结缔组织异常在这些患者中是常见的发现。
从322例颈内动脉夹层（CeAD）患者的连续登记资料中，我们识别并分析了4例有其他血管床额外夹层病史的患者。对其中3例患者的真皮结缔组织进行了电子显微镜检查。对所有4例患者的DNA进行了全外显子组测序和拷贝数变异（CNV）分析。
在所有3例接受分析的患者中，真皮活检的胶原纤维均有病理改变。1例患者携带破坏 和 基因的CNV（血管型或活动度过高型埃勒斯-当洛综合征），另1例患者携带 的CNV（家族性胸主动脉瘤和夹层）。第3例患者在 基因中有一个错义替代。
3例患者表现出真皮结缔组织的形态学改变，2例患者携带与动脉结缔组织功能障碍相关基因的致病变异。这些发现表明，在复发性动脉夹层后，无论结缔组织疾病的明显表型体征如何，都应建议进行基因检测。
