Atresia of inferior vena cava (IVC) is a rare congenital malformation associated with high risk of venous thrombosis that still has unknown etiology, although intrauterine IVC thrombosis has been suggested to be involved. The identification of IVC atresia in a case with early idiopathic venous thrombosis and antithrombin deficiency caused by the homozygous SERPINC1 c.391C > T variant (p.Leu131Phe; antithrombin Budapest 3) encouraged us to evaluate the role of this severe thrombophilia in this vascular abnormality. We have done a cross-sectional study in previously identified cohorts of patients homozygous for the Budapest 3 variant (N = 61) selected from 1118 patients with congenital antithrombin deficiency identified in two different populations: Spain (N = 692) and Hungary (N = 426). Image analysis included computed tomography and phlebography. Atresia of the IVC system was observed in 17/24 cases (70.8%, 95% confidence interval [CI]: 48.9%–87.3%) homozygous for antithrombin Budapest 3 with available computed tomography (5/8 and 12/16 in the Spanish and Hungarian cohorts, respectively), 16 had an absence of infrarenal IVC and one had atresia of the left common iliac vein. All cases with vascular defects had compensatory mechanisms, azygos-hemiazygos continuation or double IVC, and seven also had other congenital anomalies. Short tandem repeat analysis supported the specific association of the IVC system atresia with SERPINC1. We show the first evidence of the association of a severe thrombophilia with IVC system atresia, supporting the possibility that a thrombosis in the developing fetal vessels is the reason for this anomaly. Our hypothesis-generating results encourage further studies to investigate severe thrombophilic states in patients with atresia of IVC.

中文翻译：

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由纯合子抗凝血酶布达佩斯 3 变体引起的严重血栓形成倾向中下腔静脉系统闭锁的高外显率：一种新综合征的描述

下腔静脉闭锁 (IVC) 是一种罕见的先天性畸形，与静脉血栓形成的高风险相关，病因尚不明确，尽管有人建议涉及宫内 IVC 血栓形成。在由纯合子SERPINC1 c.391C > T变体（p.Leu131Phe；抗凝血酶布达佩斯 3）引起的早期特发性静脉血栓形成和抗凝血酶缺乏的病例中发现 IVC 闭锁鼓励我们评估这种严重的血栓形成倾向在这种血管异常中的作用. 我们在先前确定的布达佩斯 3 变异纯合子患者队列（N  = 61）中进行了一项横断面研究，这些患者选自在两个不同人群中确定的 1118 名先天性抗凝血酶缺乏症患者：西班牙（N  = 692）和匈牙利（N  = 426）。图像分析包括计算机断层扫描和静脉造影。在 17/24 例（70.8%，95% 置信区间 [CI]：48.9%–87.3%）抗凝血酶布达佩斯 3 纯合子病例中观察到 IVC 系统闭锁，可用计算机断层扫描（西班牙语为 5/8 和 12/16）和匈牙利队列），16 人没有肾下腔静脉，1 人左髂总静脉闭锁。所有血管缺陷病例均有代偿机制、奇半奇连续或双下腔静脉，7例还存在其他先天性异常。短串联重复分析支持 IVC 系统闭锁与SERPINC1的特定关联. 我们展示了严重血栓形成倾向与 IVC 系统闭锁相关的第一个证据，支持发育中的胎儿血管血栓形成是这种异常的原因的可能性。我们的假设结果鼓励进一步研究调查 IVC 闭锁患者的严重血栓形成状态。