We report on a novel Xq11.11 microdeletion in a patient presenting with severe mental retardation (MR), focal epilepsy, tall stature, macrocephaly, and dysmorphism. This 1.3 Mb deletion, identified using array CGH, includes a single gene with known function-ARHGEF9-plus 1 gene with unknown function and three putative genes. ARHGEF9 encodes collybistin (Cb) that plays an important role in the localization of gephyrin which is the key protein of the scaffolding system of inhibitory synapses and is essential for postsynaptic clustering of both GABA(A) and glycine receptors. Cb-deficient male mice show reduced exploratory behavior, impaired spatial learning, increased anxiety scores, and reduction of gephyrin-dependent GABA receptor clusters in amygdala and hippocampus. Mutations or disruption of ARHGEF9 due to chromosomal rearrangements have been found in three patients with various clinical presentations: nevertheless, all 3 presented with MR and 2 with epilepsy. The case we report on provides further evidence for the role of ARHGEF9 in cognitive development. The other phenotypic features in our patient, including macrosomia and dysmorphism, may also be related to the loss of this gene. Alternatively, they may be consequences of the loss of one or more of the other genes located within the deletion or of the disruption of sequences regulating neighboring genes. Additional case reports with identical or overlapping deletions would help in defining the phenotype associated with ARHGEF9 haploinsufficiency.

Vigabatrin is an antiepileptic drug that produces intramyelinic edema in several animal models. This study investigates the effect of vigabatrin on the developing human brain. The authors retrospectively blindly review 34 brain magnetic resonance imaging of 22 epileptic infants (age: 9 +/- 1 months) that received vigabatrin, focusing on the presence of hyperintensity on T2- and diffusion-weighted images. Patients treated with vigabatrin displayed significant magnetic resonance imaging hyperintensity of basal ganglia and brain stem (P < .001, Wilcoxon test). This hyperintensity was transient and maximal 3 to 6 months after the beginning of vigabatrin. Hyperintensity was independent from duration and type of epilepsy, and from the presence or absence of seizures. The authors conclude that vigabatrin treatment is associated with transient hypersignal of the basal ganglia and brain stem in epileptic infants. Such transient hyperintensity is likely to be age-dependent and time-dependent because it has never been observed in adult patients.

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Learning disability and cerebral palsy are often related to factors present before birth. We report three patients (two with schizencephaly, one with unilateral cerebellar agenesis) in whom the timing of an insult to the foetus was known. In the first case, the mother had a trauma at 16 weeks of pregnancy and schizencephaly was discovered in the male infant associated with a left hemiplegia. In the second child, amniocentesis performed at 16 weeks into pregnancy may have been responsible for the same cortical anomaly. In the third case, sequential foetal echographies clearly demonstrated that an apparent unilateral cerebellar agenesis was related to an haemorrhagic event secondary to cerebellar trauma that occurred at 19 weeks of pregnancy. It is suggested that these brain malformations are related to an ischemic mechanism or a traumatic event in foetal life.

Learning disability and cerebral palsy are often related to factors present before birth. We report three patients (two with schizencephaly, one with unilateral cerebellar agenesis) in whom the timing of an insult to the foetus was known. In the first case, the mother had a trauma at 16 weeks of pregnancy and schizencephaly was discovered in the male infant associated with a left hemiplegia. In the second child, amniocentesis performed at 16 weeks into pregnancy may have been responsible for the same cortical anomaly. In the third case, sequential foetal echographies clearly demonstrated that an apparent unilateral cerebellar agenesis was related to an haemorrhagic event secondary to cerebellar trauma that occurred at 19 weeks of pregnancy. It is suggested that these brain malformations are related to an ischemic mechanism or a traumatic event in foetal life.

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