Annual Review of Pathology: Mechanisms of Disease ( IF 28.4 ) Pub Date : 2017-01-30 00:00:00 , DOI: 10.1146/annurev-pathol-052016-100138 Philip H. Iffland 1 , Peter B. Crino 2
Focal cortical dysplasias (FCDs) are malformations of cortical development (MCDs) that are highly associated with medication-resistant epilepsy and are the most common cause of neocortical epilepsy in children. FCDs are a heterogeneous group of developmental disorders caused by germline or somatic mutations that occur in genes regulating the PI3K/Akt/mTOR pathway—a key pathway in neuronal growth and migration. Accordingly, FCDs are characterized by abnormal cortical lamination, cell morphology (e.g., cytomegaly), and cellular polarity. In some FCD subtypes, balloon cells express proteins typically seen in neuroglial progenitor cells. Because recurrent intractable seizures are a common feature of FCDs, epileptogenic electrophysiological properties are also observed in addition to local inflammation. Here, we will summarize the current literature regarding FCDs, addressing the current classification system, histopathology, molecular genetics, electrophysiology, and transcriptome and cell signaling changes.
中文翻译:
局灶性皮质发育不良:基因突变,细胞信号转导和治疗意义。
局灶性皮质发育不良(FCD)是皮质发育(MCD)的畸形,与药物耐受性癫痫高度相关,是儿童新皮质癫痫的最常见原因。FCD是由种系或体细胞突变引起的一组异质性发育障碍,这些突变发生在调节PI3K / Akt / mTOR途径的基因中,而PI3K / Akt / mTOR途径是神经元生长和迁移的关键途径。因此,FCD的特征在于异常的皮质层合,细胞形态(例如,细胞肿大)和细胞极性。在某些FCD亚型中,球囊细胞表达通常在神经胶质祖细胞中可见的蛋白质。由于反复发作的顽固性癫痫发作是FCD的共同特征,因此除了局部炎症外,还观察到了癫痫发生的电生理特性。这里,