PTEN失活突变是巨脑症最常见的原因之一。PI3K/AKT/MTOR信号通路中其他节点的激活突变已被确认为皮质脑发育异常的频繁原因。仅最近才将PTEN与皮质脑发育异常联系起来，并且对其预后意义的分析有限。对20名存在PTEN致病性或可能致病性突变且脑磁共振成像显示存在皮质脑发育异常的参与者进行了回顾性神经影像学分析和详细的病历回顾。神经影像学分析揭示了四种主要的脑脏类型，分别为半巨脑症、局灶性皮质发育异常、多微脑回和一种较轻的类别，命名为“复杂脑沟模式的巨头症”。尽管有高比例（90%）的参与者在出现时存在神经发育异常，但预后各异，其中超过一半的参与者预后良好。与以往研究一致，39%的参与者患有自闭症谱系障碍，而纯多微脑回或纯复杂脑沟模式表型的参与者中有19%出现了癫痫。巨脑症和全身超发育是常见的，但PTEN-错构瘤病综合征的其他全身特征在超过三分之一的参与者中不存在。PTEN失活突变导致脑皮质发育异常的谱系多样。有必要进行进一步研究以阐明每种脑脏类型的预后意义，但总体而言，尽管神经发育疾病负担较重，长期预后可能是良好的。在巨脑症和脑皮质发育异常的情况下，甚至在没有其他发现（包括认知障碍）的情况下，应考虑PTEN突变的种系检测。版权所有 © 2023 Elsevier Inc. 保留所有权利。

Inactivating mutations in PTEN are among the most common causes of megalencephaly. Activating mutations in other nodes of the PI3K/AKT/MTOR signaling pathway are recognized as a frequent cause of cortical brain malformations. Only recently has PTEN been associated with cortical malformations, and analyses of their prognostic significance have been limited.Retrospective neuroimaging analysis and detailed chart review were conducted on 20 participants identified with pathogenic or likely pathogenic mutations in PTEN and a cortical brain malformation present on brain magnetic resonance imaging.Neuroimaging analysis revealed four main cerebral phenotypes-hemimegalencephaly, focal cortical dysplasia, polymicrogyria (PMG), and a less severe category, termed "macrocephaly with complicated gyral pattern" (MCG). Although a high proportion of participants (90%) had neurodevelopmental findings on presentation, outcomes varied and were favorable in over half of participants. Consistent with prior work, 39% of participants had autism spectrum disorder and 19% of participants with either pure-PMG or pure-MCG phenotypes had epilepsy. Megalencephaly and systemic overgrowth were common, but other systemic features of PTEN-hamartoma tumor syndrome were absent in over one-third of participants.A spectrum of cortical dysplasias is present in individuals with inactivating mutations in PTEN. Future studies are needed to clarify the prognostic significance of each cerebral phenotype, but overall, we conclude that despite a high burden of neurodevelopmental disease, long-term outcomes may be favorable. Germline testing for PTEN mutations should be considered in cases of megalencephaly and cortical brain malformations even in the absence of other findings, including cognitive impairment.Copyright © 2023 Elsevier Inc. All rights reserved.