title: Focal Cortical Dysplasia: Gene Mutations, Cell Signaling, and Therapeutic Implications.
abstract: 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.
authors.affiliation: Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140; email: philip.iffland@temple.edu.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Iffland
authors.affiliation: Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland 21201; email: pcrino@som.umaryland.edu.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Crino
mesh_terms: D000818:Animals; D006801:Humans; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
keywords: developmental biology; focal cortical dysplasia electrophysiology; inflammation; mTOR; mTORopathy; molecular genetics; transcriptome