Thromboembolism and Congenital Malformations
Thromboembolism and Congenital Malformations
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DOI：
10.1001/jamaophthalmol.2013.1111
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发表时间：
2013-04-01
影响因子：
8.1
通讯作者：
Robert, Matthieu P.
中科院分区：
文献类型：
--
作者：
Parsa, Cameron F.;Robert, Matthieu P.
目的：探讨各种散发性先天性畸形的病理生理机制。方法：通过归纳和演绎分析将畸形偏侧性与胸部解剖不对称联系起来，对女性优势畸形进行批判性分析，并将血管生长中的流体动压梯度概念应用于随后的指导组织支架的开发，以促进细胞增殖、分化和凋亡。结果：Duane综合征可能在第六神经干局灶性血管损伤伴轴突变性后发生，从而允许从第三神经轴突到外侧直肌的替代神经支配。致病性纤维蛋白凝块可能起源于静脉系统，并通过生理右至左分流矛盾地迁移，或者它们可能直接来自心脏。因此，Duane综合征的单侧、左侧和女性优势是由于胸部解剖结构的不对称和血栓形成的危险因素造成的。栓塞也可能改变局部血流动压梯度，导致胎儿血管代偿性扩大和持续存在，并可能失调组织生长。在眼睛内，这导致彼得斯畸形、单侧先天性白内障和牵牛花椎间盘畸形的形式，所有这些都发生在颈动脉的血管区域，在女孩中也有左侧受累的倾向。大多数异常的神经支配错误现象（例如，眨眼综合征、鳄鱼撕裂综合征、布朗综合征和先天性纤维化综合征），以及通过外推，非头部解剖结构（包括肢体）的发育不全或发育不良也可以类似地解释。这种畸形将更频繁地发生在血栓形成的条件下，如那些由沙利度胺诱导。结论：纤维蛋白栓塞和局灶性灌注不足可以解释许多散发性先天性畸形的发生。
Objective: To propose a pathophysiologic mechanism to unify a variety of disparate sporadic congenital malformations.Methods: Inductive and deductive analyses to correlate malformation laterality with asymmetries in thoracic anatomy, critical analysis of malformations with female predominance, and concepts of hydrodynamic pressure gradients in vascular growth were applied to the ensuing development of guiding tissue scaffolds for cellular proliferation, differentiation, and apoptosis.Results: Duane syndrome may develop following a focal vascular insult to the sixth nerve trunk with axonal degeneration, allowing for substitutive innervation from third nerve axons to the lateral rectus muscle. Causative fibrin clots may originate from the venous system and paradoxically migrate through physiological right-to-left shunts, or they may arise directly from the heart. Hence, the unilateral, left-sided, and female predominance of Duane syndrome results from the asymmetry in the thoracic anatomy and from thrombosis risk factors. Embolic occlusions may also alter local hemody-namic pressure gradients, leading to the compensatory enlargement and persistence of the fetal vasculature and may dysregulate tissue growth. Within the eye, this results in forms of Peters anomaly, unilateral congenital cataracts, and the morning glory disc anomaly, all in the vascular territory of the carotid arteries that also share a propensity for left-sided involvement in girls. Most aberrant misinnervation phenomena (eg, jaw-winking syndrome, crocodile tear syndrome, Brown syndrome, and congenital fibrosis syndrome) and, by extrapolation, the hypoplasia or dysgenesis of noncephalic anatomical structures (including limbs) may be similarly explained. Such malformations will occur more frequently under thrombogenic conditions, such as those induced by thalidomide.Conclusions: Fibrin emboli and focal hypoperfusion may explain the development of many sporadic congenital malformations.