<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders

Phenothiazine-induced sleep apneas in normal infants

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Anterior Fontanelle Pressure Variations During Sleep in Healthy Infants

info:eu-repo/semantics/publishe

Technical recommendations and interpretation guidelines for electroencephalography for premature and full-term newborns

Electroencephalography (EEG) of neonatal patients is amongst the most valuable diagnostic and prognostic tool. EEG recordings, acquired at the bedside of infants, evaluate brain function and the maturation of premature and extremely premature infants. Strict conditions of acquisition and interpretation must be respected to guarantee the quality of the EEG and ensure its safety for fragile children. This article provides guidance for EEG acquisition including: (1) the required equipment and devices, (2) the modalities of installation and asepsis precautions, and (3) the digital signal acquisition parameters to use during the recording. The fundamental role of a well-trained technician in supervising the EEG recording is emphasized. In parallel to the acquisition recommendations, we present a guideline for EEG interpretation and reporting. The successive steps of EEG interpretation, from reading the EEG to writing the report, are described. The complexity of the EEG signal in neonates makes artefact detection difficult. Thus, we provide an overview of certain characteristic artefacts and detail the methods for eliminating them.SCOPUS: re.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Identification of prenatal behavioral patterns of the gross motor movements within the early stages of fetal development

Copyright © 2016 John Wiley & Sons, Ltd. Little is known about the manner in which motor behavior of the gross motor movements develops in early fetal period. Therefore, the goal of this study was to identify and classify the fetal distinct behavior patterns of the gross motor movements qualitatively in gestational weeks 10 through 17 (N = 69 fetuses). Using our unique Systematic Observation and Analysis Procedure based on conventional 2D ultrasound, we were able to identify the distinct behavior patterns with respect to the fetus' orientation (e.g., postural position and additional support by uterine wall) in real time and therefore distinguish 12 categories of behavioral patterns. The kappa coefficient for this procedure was 0.82, indicating high interobserver reliability. Interestingly, six of these 12 categories were not observed in gestational week 10–11, whereas all 12 movement categories were present in gestational week 16–17. Importantly, the occurrence of early development of gross motor control in utero emerges in the presence of dynamic and interactive environmental factors, providing new insights into the fundamental aspects of developmental motor behavior in the growing infant. Highlights: We developed a system for real-time monitoring of behavioral patterns of the gross motor movements with respect to the fetus' intrauterine orientation using a two-step, non-invasive observation protocol. Our monitoring system allowed us to detect twelve separate categories of distinct behavioral patterns of the gross motor movements in gestational week 10–17. Gross motor control develops in the early fetal period and is affected by the presence of dynamic and interactive environmental factors.status: publishe

Identification of prenatal behavioral patterns of the gross motor movements within the early stages of fetal development

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Prevalence of cerebral palsy and factors associated with cerebral palsy subtype: A population-based study in Belgium.

AIM: To report on the prevalence, neuroimaging patterns, and function of children with cerebral palsy (CP) in Belgium for birth years 2007-2012, and identify distinctive risk indicators and differences in outcome between CP subtypes. METHODS: Antenatal and perinatal/neonatal factors, motor and speech function, associated impairments, and neuroimaging patterns were extracted from the Belgian Cerebral Palsy Register. Prevalence was estimated per 1000 (overall, ante/perinatal, spastic, dyskinetic CP) or 10,000 (post-neonatal, ataxic CP) live births. Multinomial logistic regression analyses were performed to ascertain the effects of antenatal/perinatal/neonatal factors and neuroimaging patterns on the likelihood of dyskinetic or ataxic CP relative to spastic CP, and test the likelihood of the occurrence of impaired motor and speech function and associated impairments in dyskinetic or ataxic CP relative to spastic CP. RESULTS: In total, 1127 children with CP were identified in Belgium. The birth prevalence of overall CP was 1.48 per 1000 live births. The likelihood of dyskinetic CP increases if the child was born to a mother aged ≥35 years, mechanically ventilated, and had predominant grey matter injury, while an increased likelihood of ataxic CP is associated with ≥2 previous deliveries. Children with dyskinetic and ataxic CP are more likely to function with impairments in motor, speech, and intellectual abilities. CONCLUSION: Distinctive risk indicators and differences in outcome between CP subtypes were identified. These factors can be incorporated into clinical practice to facilitate early, accurate, and reliable classification of CP subtype, and may lead to individually tailored neonatal care and other (early) intervention options