胚胎发育过程中，神经前体细胞的增殖和分化失调会引发先天性脑畸形，这些畸形是导致2岁以下患者发生病症和死亡的常见原因。动物模型为导致先天性脑畸形的疾病发病机制提供了大量的见解。但是，不同物种之间的脑结构差异限制了将这些见解直接应用于人体研究。近年来，使用三维（3D）培养系统从人类胚胎干细胞（hESCs）或人类诱导多能干细胞（hiPSCs）生成的脑器官样结构已被用来模拟人脑发育的结构和功能。因此，我们旨在总结通过器官样体模拟的不同先天性脑畸形，并讨论该模型揭示先天性脑畸形的细胞和分子机制的能力。 使用PubMed和Web of Science Core Collection检索了2000年7月1日至2022年7月1日发表的文献。关键词包括与脑器官样结构和先天性脑畸形相关的术语，以及各种不同的脑畸形名称。自组装的3D聚集体已被用于重现人脑结构畸形，如小头畸形、大头畸形、平滑脑（LIS）和室旁结节异位症（PH）。使用特定疾病的脑器官样结构揭示了引起先天性脑畸形的机制的前所未有的细节。 本综述总结了脑器官样结构技术的建立和发展，并概述了它们在先天性脑畸形建模中的应用。虽然仍需克服一些困难，但使用脑器官样结构大大扩展了我们揭示先天性脑畸形的病因学的能力。与现有方法相比，结合尖端技术使得对先天性脑疾病患者进行更准确的诊断和越来越个性化的靶向治疗发展成为可能。 2023年Translational Pediatrics，保留所有权利。

During embryonic development, the dysregulation of the proliferation and differentiation of neuronal progenitors triggers congenital brain malformations. These malformations are common causes of morbidity and mortality in patients younger than 2 years old. Animal models have provided considerable insights into the etiology of diseases that cause congenital brain malformations. However, the interspecies differences in brain structure limit the ability to transfer these insights directly to studies of humans. In recent years, brain organoids generated from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) using a 3-dimensional (3D) culture system have been used to resemble the structure and function of a developing human brain. Therefore, we aimed to summarize the different congenital brain malformations that have been modeled by organoids and discuss the ability of this model to reveal the cellular and molecular mechanisms of congenital brain malformations.A comprehensive search was performed using PubMed and Web of Science's Core Collection for literature published from July 1, 2000 to July 1, 2022. Keywords included terms related to brain organoids and congenital brain malformations, as well as names of individual malformations.The self-assembled 3D aggregates have been used to recapitulate structural malformations of human brains, such as microcephaly, macrocephaly, lissencephaly (LIS), and periventricular nodular heterotopia (PH). The use of disease-specific brain organoids has revealed unprecedented details of mechanisms that cause congenital brain malformations.This review summarizes the establishment and development of brain organoid technologies and provides an overview of their applications in modeling congenital brain malformations. Although several hurdles still need to be overcome, using brain organoids has greatly expanded our ability to reveal the pathogenesis of congenital brain malformations. Compared with existing methods, the combination with cutting-edge technologies enables a more accurate diagnosis and development of increasingly personalized targeted therapy for patients with congenital brain diseases.2023 Translational Pediatrics. All rights reserved.