Expansion of NEUROD2 phenotypes to include developmental delay without seizures.

De novo heterozygous variants in the brain-specific transcription factor Neuronal Differentiation Factor 2 (NEUROD2) have been recently associated with early-onset epileptic encephalopathy and developmental delay. Here, we report an adolescent with developmental delay without seizures who was found to have a novel de novo heterozygous NEUROD2 missense variant, p.(Leu163Pro). Functional testing using an in vivo assay of neuronal differentiation in Xenopus laevis tadpoles demonstrated that the patient variant of NEUROD2 displays minimal protein activity, strongly suggesting a loss of function effect. In contrast, a second rare NEUROD2 variant, p.(Ala235Thr), identified in an adolescent with developmental delay but lacking parental studies for inheritance, showed normal in vivo NEUROD2 activity. We thus provide clinical, genetic, and functional evidence that NEUROD2 variants can lead to developmental delay without accompanying early-onset seizures, and demonstrate how functional testing can complement genetic data when determining variant pathogenicity.

Visually evoked potentials (VEPs) across the visual field in hearing and deaf cats.

Introduction: Congenitally deaf cats perform better on visual localization tasks than hearing cats, and this advantage has been attributed to the posterior auditory field. Successful visual localization requires both visual processing of the target and timely generation of an action to approach the target. Activation of auditory cortex in deaf subjects during visual localization in the peripheral visual field can occur either via bottom-up stimulus-driven and/or top-down goal-directed pathways. Methods: In this study, we recorded visually evoked potentials (VEPs) in response to a reversing checkerboard stimulus presented in the hemifield contralateral to the recorded hemisphere in both hearing and deaf cats under light anesthesia. Results: Although VEP amplitudes and latencies were systematically modulated by stimulus eccentricity, we found little evidence of changes in VEP in deaf cats that can explain their behavioral advantage. A statistical trend was observed, showing larger peak amplitudes and shorter peak latencies in deaf subjects for stimuli in the near- and mid-peripheral field. Additionally, latency of the P1 wave component had a larger inter-sweep variation in deaf subjects. Discussion: Our results suggested that cross-modal plasticity following deafness does not play a major part in cortical processing of the peripheral visual field when the "vision for action" system is not recruited.