Greenwood Genetic Center, J. C. Self Research Institute of Human Genetics, Greenwood, South Carolina, USA.
Am J Med Genet A. 2021 May;185(5):1379-1387. doi: 10.1002/ajmg.a.62103. Epub 2021 Jan 31.
Decades of clinical, pathological, and epidemiological study and the recent application of advanced microarray and gene sequencing technologies have led to an understanding of the causes and pathogenesis of most recognized patterns of malformation. Still, there remain a number of patterns of malformation whose pathogenesis has not been established. Six such patterns of malformation are sirenomelia, VACTERL association, OEIS complex, limb-body wall defect (LBWD), urorectal septum malformation (URSM) sequence, and MURCS association, all of which predominantly affect caudal structures. On the basis of the overlap of the component malformations, the co-occurrence in individual fetuses, and the findings on fetal examination, a common pathogenesis is proposed for these patterns of malformation. The presence of a single artery in the umbilical cord provides a visible clue to the pathogenesis of all cases of sirenomelia and 30%-50% of cases of VACTERL association, OEIS complex, URSM sequence, and LBWD. The single artery is formed by a coalescence of arteries that supply the yolk sac, arises from the descending aorta high in the abdominal cavity, and redirects blood flow from the developing caudal structures of the embryo to the placenta. This phenomenon during embryogenesis is termed vitelline vascular steal.
数十年的临床、病理和流行病学研究以及最近应用先进的微阵列和基因测序技术，使我们对大多数公认的畸形模式的病因和发病机制有了一定的了解。然而，仍有一些畸形模式的发病机制尚未确定。其中六种畸形模式为并肢畸形、VACTERL 联合征、OEIS 复合征、肢体-体壁缺陷（LBWD）、尿道直肠隔膜畸形（URSM）序列和 MURCS 联合征，这些畸形模式主要影响尾部结构。基于组成性畸形的重叠、个体胎儿的同时出现以及胎儿检查的结果，提出了这些畸形模式的共同发病机制。脐带中存在单根动脉为所有并肢畸形和 30%-50%的 VACTERL 联合征、OEIS 复合征、URSM 序列和 LBWD 的发病机制提供了一个明显的线索。这根单根动脉是由供应卵黄囊的动脉融合而成，起源于腹腔内较高的降主动脉，并将血流从胚胎发育中的尾部结构重新引导至胎盘。这种胚胎发生过程中的现象被称为卵黄血管盗血。
