Phenotypic variability in human embryonic holoprosencephaly in the Kyoto collection
Phenotypic variability in human embryonic holoprosencephaly in the Kyoto collection
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DOI：
10.1002/bdra.20048
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发表时间：
2004-08-01
影响因子：
--
通讯作者：
Shiota, K
中科院分区：
文献类型：
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作者：
Yamada, S;Uwabe, C;Shiota, K
背景：无前脑畸形(HPE)是一种与特殊的颅面部畸形发生相关的最常见的脑发育障碍。虽然已经报道了大量的出生后病例，但其早期发病机制尚不清楚。我们对200多个HPE人类胚胎进行了大体和组织学检查，并研究了它们的表型变异性和阶段特异性特征。方法：在京都人类胚胎采集库的44,000多个人类胚胎中，221个胚胎被诊断为HPE。它们的发育阶段从卡内基阶段(CS)13到CS 23。对它们进行大体检查，并进行连续切片进行详细的组织学分析。结果：CS18后HPE胚胎可分为完全性(真性)单眼斜视、同眼(单眼裂隙部分融合)、双眼近对置(可能是筛头畸形和头颅畸形的前驱)和轻度HPE合并正中唇裂(前颌骨发育不全)。在CS 13-17，当面部形态发生尚未完成时，HPE胚胎具有某些面部特征，这些特征是这些阶段所特有的，不同于较老的HPE胚胎。在HPE胚胎中，包括脑下垂体在内的大脑中线结构缺乏或严重发育不良。CS 18术后2例出现完全性屈光不正，早期无1例。结论：首次对人胚胎HPE的早期发育进行了系统研究。根据最近对突变实验动物的研究，讨论了HPE中头面部异常，特别是眼异常的发病机制。(C)2004年Wiley-Liss公司
BACKGROUND: Holoprosencephaly (HPE) is one of the most common developmental disorders of the brain associated with specific craniofacial dysmorphogenesis. Although numerous postnatal cases have been reported, early phases of its pathogenesis are not well understood. We examined over 200 cases of HPE human embryos both grossly and histologically, and studied their phenotypic variability and stage-specific characteristics. METHODS: Among over 44,000 human embryos in the Kyoto Collection of Human Embryos, 221 embryos have been diagnosed as HPE. Their developmental stages ranged from Carnegie stage (CS) 13 to CS 23. They were examined grossly and were also serially sectioned for detailed histological analysis. RESULTS: HPE embryos after CS 18 were classified into complete (true) cyclopia, synophthalmia (partially fused eyes in a single eye fissure), closely apposed separate eyes (possible forerunners of ethmocephaly and cebocephaly), and milder HPE with median cleft lip (premaxillary agenesis). At CS 13-17, when facial morphogenesis is not completed, HPE embryos had some facial characteristics that are specific to these stages and different from those in older HPE embryos. The midline structures of the brain, including the pituitary gland, were lacking or seriously hypoplastic in HPE embryos. Complete cyclopia was found in two cases after CS 18 but none at earlier stages. CONCLUSIONS: The early development of HPE in human embryos was systematically studied for the first time. The pathogenesis of craniofacial abnormalities, especially eye anomalies, in HPE was discussed in the light of recent studies with mutant laboratory animals. (C) 2004 Wiley-Liss, Inc.