Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly

Loss ofEmx2function leads to ectopic expression ofWnt1in the developing telencephalon and cortical dysplasia

“…Alterations of Wnt pathway signaling have been described within human cortical resections containing focal intra-cortical dysplasias, but the presence of heterotopias was not addressed in this study (Cotter et al, 1999). Loss-of-function mutations in EMX2 have been described in individuals with the radiological diagnosis of schizencephaly, a rare cortical dysplasia syndrome (Brunelli et al, 1996;Faiella et al, 1997;Granata et al, 1997). However, further work will be required to determine whether EMX2 loss in these individuals is associated with heterotopias or MZ/SP abnormalities as the neuroimaging techniques used to identify the individuals lacked the resolution to detect such microscopic lesions and the neuropathological findings in these cases have not been described.…”

Mouse orthologue of ARX, a gene mutated in several X‐linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons

“…Among them, ARX is the only gene involved is such disease, coding for a transcription factor. Of interest, another homeobox containing gene, EMX2, has been implicated in schizencephaly, a rare human congenital disorder characterized by a fullthickness clefts within the cerebral hemispheres, which are believed to arise from an abnormal pattern of neural migration and proliferation during development (Brunelli et al, 1996). Notably, murine Emx2 mutant cortex displays abnormal layering (Mallamaci et al 2000a) and frequent heterotopias and cortical dysplasia (Ligon et al, 2003).…”

Bilateral Schizencephaly Type II

“…Different theories have been proposed for the supposed fetal brain damage like a vascular injury leading to an infarction in the area of germinal matrix, cytomegalovirus infection, EMX2 gene mutation, herpes virus, maternal trauma, teratogens, alcohol and drug abuse, warfarin, and monozygotic twin interactions. 6 Therefore, it is considered to be secondary to multiple factors, leading to a final common manifestation of abnormal neuronal migration. However, in our case no known aetiological factor could be identified.…”