Neural tube defects--disorders of neurulation and related embryonic processes.
Neural tube defects--disorders of neurulation and related embryonic processes.
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DOI：
10.1002/wdev.71
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发表时间：
2013-03
影响因子：
--
通讯作者：
Greene, Nicholas D. E.
中科院分区：
文献类型：
--
作者：
Copp, Andrew J.;Greene, Nicholas D. E.
神经管缺陷 (NTD) 是一种严重的先天畸形，每 1000 次妊娠中就有 1 人患有神经管缺陷。 “开放性”NTD 是由于初级神经发育失败造成的，如无脑畸形、脊髓脊膜膨出（开放性脊柱裂）和颅骨劈裂。子宫内持续开放的神经管变性导致病变水平以下的神经功能丧失。 “闭合性”NTD 是皮肤覆盖的脊髓结构疾病，范围从无症状的隐性脊柱裂到严重的脊髓束缚，通常可追溯到二级神经系统的破坏。 “突出”NTD 是指脑膜（无论有或没有大脑或脊髓组织）通过颅骨或脊柱的病理性开口外露（例如脑膨出和脑膜膨出）。 NTD 具有多因素病因，基因和环境因素相互作用决定个体畸形风险。虽然超过 200 个突变基因会导致小鼠出现开放性 NTD，但人们对人类 NTD 的遗传原因知之甚少。最近的证据表明，部分病例涉及平面细胞极性信号通路的基因。 NTD 的胚胎发育很复杂，在身体轴的不同水平上有不同的细胞和分子机制运作。分子调控事件包括 BMP 和 Sonic hedgehog 通路，它们与神经板弯曲的控制有关。在证明叶酸作为围孕期补充剂可以预防许多病例后，NTD 的一级预防已在临床上实施。然而，并非所有 NTD 都对叶酸有反应，因此需要辅助治疗来预防这种叶酸抗性类别。
Neural tube defects (NTDs) are severe congenital malformations affecting 1 in every 1000 pregnancies. ‘Open’ NTDs result from failure of primary neurulation as seen in anencephaly, myelomeningocele (open spina bifida) and craniorachischisis. Degeneration of the persistently open neural tube in utero leads to loss of neurological function below the lesion level. ‘Closed’ NTDs are skin-covered disorders of spinal cord structure, ranging from asymptomatic spina bifida occulta to severe spinal cord tethering, and usually traceable to disruption of secondary neurulation. ‘Herniation’ NTDs are those in which meninges, with or without brain or spinal cord tissue, become exteriorised through a pathological opening in the skull or vertebral column (e.g. encephalocele and meningocele). NTDs have multifactorial etiology, with genes and environmental factors interacting to determine individual risk of malformation. While over 200 mutant genes cause open NTDs in mice, much less is known about the genetic causation of human NTDs. Recent evidence has implicated genes of the planar cell polarity signalling pathway in a proportion of cases. The embryonic development of NTDs is complex, with diverse cellular and molecular mechanisms operating at different levels of the body axis. Molecular regulatory events include the BMP and Sonic hedgehog pathways which have been implicated in control of neural plate bending. Primary prevention of NTDs has been implemented clinically following the demonstration that folic acid, when taken as a peri-conceptional supplement, can prevent many cases. Not all NTDs respond to folic acid, however, and adjunct therapies are required for prevention of this folic acid-resistant category.