Feedforward motor control in developmental dyslexia and developmental coordination disorder: Does comorbidity matter?

BACKGROUND AND AIM: Feedforward and online controls are two facets of predictive motor control from internal models, which is suspected to be impaired in learning disorders. We examined whether the feedforward component is affected in children (8-12 years) with developmental dyslexia (DD) and/or with developmental coordination disorder (DCD) compared to typically developing (TD) children. METHODS: Children underwent a bimanual unloading paradigm during which a load supported to one arm, the postural arm, was either unexpectedly unloaded by a computer or voluntary unloaded by the subject with the other arm. RESULTS: All children showed a better stabilization (lower flexion) of the postural arm and an earlier inhibition of the arm flexors during voluntary unloading, indicating anticipation of unloading. Between-group comparisons of kinematics and electromyographic activity of the postural arm revealed that the difference during voluntary unloading was between DD-DCD children and the other groups, with the former showing a delayed inhibition of the flexor muscles. CONCLUSION: Deficit of the feedforward component of motor control may particularly apply to comorbid subtypes, here the DD-DCD subtype. The development of a comprehensive framework for motor performance deficits in children with learning disorders will be achieved only by dissociating key components of motor prediction and focusing on subtypes and comorbidities.

De novo Xq11.11 microdeletion including ARHGEF9 in a boy with mental retardation, epilepsy, macrosomia, and dysmorphic features.

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.

Transient brain magnetic resonance imaging hyperintensity in basal ganglia and brain stem of epileptic infants treated with vigabatrin.

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.