Familial schizencephaly associated with EMX2 mutation

Abstract

We describe two brothers aged 8 and 10 affected by severe bilateral schizencephaly, carrying an identical point mutation of the homeobox gene EMX2. Both children had severe neurologic deficits and mental retardation, although they differed in the anatomic extent of the brain malformation and in the severity of the clinical picture. The present findings, together with the reported cases of schizencephaly associated with EMX2 mutations, support the hypothesis that, at least in some cases, schizencephalies are determined by deleterious mutations of this homeobox gene. The different morphoclinical pictures suggest that, besides the EMX2 mutation, other factors are relevant in determining the severity of the brain malformation and clinical picture.

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.…”

Ultrasound Diagnosis of Congenital Brain Anomalies

“…Familial cases have been reported, suggesting a possible genetic origin within a group of neuronal migration disorders (Guerrini & Carrozzo, 2001). Recent studies have linked schizencephaly with a mutated gene called EMX2 homeobox gene (Guerrini & Carrozzo, 2001;Granata et al, 1997). If the gene EMX-2 is missing or defective, nerve cell growth and migration will not occur normally and lead to the formation of the clefts associated with schizencephaly.…”

Aspectos clínicos em 16 pacientes com diagnóstico tomográfico de esquizencefalia

“…Dubey et al (7) have reported the cardinal characteristics of schizencephaly: a hemispheric cleft delimited by an usually bilateral ependymal-pial sheath in the perisylvian region; a cleft lined by gray-matter linking the subarachnoid space with the ependyma of the lateral ventricle, and the association with multiple intracranial anomalies such as polymicrogyria, heterotopias, absence of pellucid septum, optic nerve hyperplasia and corpus callosum agenesia. The majority of cases described are of a sporadic nature, although there are reports on familial cases (3,6,11) . Some authors (2,3,6) have described homeotic gene EMX2 (Empty Spiracles, Drosophila, 2, Homolog of) mutations in patients with schizencephaly.…”