ABSTRACTRapid eye movement (REM) sleep, also known as paradoxical sleep (PS), was first identified in humans and cats in the late 1950s. It is hypothesized to contribute to brain development by providing endogenous neural activity patterns that coincide with critical periods of maturation. We summarize the remarkable alterations in polysomnographic data, EEG power spectral analysis, and behavioural patterns during early‐life REM sleep, as well as the subsequent maturation of these features and the development of regulatory mechanisms. REM sleep disturbances in early life are linked to neurodevelopmental disorders. Our review aims to elucidate changes in the main characteristics during REM sleep development and its evolutionary connection with brain development, ultimately providing a basis for promoting the prevention and treatment of various neurodevelopmental disorders.

No abstract is available for this article.

The meta-analysis generated a forest plot using random-effects model for assessing Vineland-II Adaptive Behavioral Composite score shows no significant improvement in symptoms with V1a receptor antagonists in ASD.

NR2F1 pathogenetic variants are associated with the Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Recent studies indicate that BBSOAS patients not only have visual impairments but may also have developmental delays, hypotonia, thin corpus callosum and epileptic seizures. However, reports of BBSOAS occurrence along with infantile epileptic spasm syndrome (IESS) are rare. Here, we report three cases involving children with IESS and BBSOAS caused by de novo NR2F1 pathogenetic variants and summarize the genotype, clinical characteristics, diagnosis and treatment of them. All three children experienced epileptic spasms and global developmental delays, with brain Magnetic Resonance Imaging (MRI) suggesting abnormalities (thinning of the corpus callosum or widened extracerebral spaces) and two of the children exhibiting abnormal visual evoked potentials. Our findings indicate that new missense NR2F1 pathogenetic variants may lead to IESS with abnormal visual evoked potentials. Thus, clinicians should be aware of the Bosch-Boonstra-Schaaf optic atrophy syndrome and regular monitoring of the fundus, and the optic nerve is necessary during follow-up.

Copper (Cu) and zinc (Zn) are important trace elements for the growth and development of children. In Wilson disease (WD), impaired Cu metabolism may affect growth. This study was conducted to evaluate the height and weight of children with neurological WD and correlate these with serum Cu, Zn, and insulin-like growth factor-I (IGF-I). This prospective cohort study was conducted in a tertiary care teaching institute. Children with neurologic WD were included. The height, weight, and body-mass index of each child were measured and categorized according to the revised national growth chart. Serum Cu, Zn, calcium, alkaline phosphatase, albumin, thyroid-stimulating hormone, and urinary-Cu were measured. Serum IGF-1 was measured by enzyme-linked immunosorbent assay. The relationship between height and weight with trace elements and IGF was analyzed using parametric or non-parametric tests. There were 52 children (5-18 years) with neurologic WD. Thirty-six (69.2%) children had normal height, 12 (23.1%) were tall, and 4 (7.7%) were stunted. Forty-six (88.5%) children had normal weight and six (11.5%) children were underweight. IGF-1 correlated with height, weight, duration of treatment, and serum Zn level. About 15.4% of children had stunting and/or wasting, which was associated with low levels of serum IGF-I, Zn, and calcium. Stunting and/or wasting occurs in 15.4% of children with neurologic WD and is associated with reduced serum IGF-I, Zn, and calcium concentration. Adjunctive Zn and calcium treatment may help in achieving normal growth.

Cortical development depends on neuronal migration of both excitatory and inhibitory interneurons. Neuronal migration disorders (NMDs) are conditions characterised by anatomical cortical defects leading to varying degrees of neurocognitive impairment, developmental delay and seizures. Refractory epilepsy affects 15 million people worldwide, and it is thought that cortical developmental disorders are responsible for 25% of childhood cases. However, little is known about the epidemiology of these disorders, nor are their aetiologies fully understood, though many are associated with sporadic genetic mutations. In this review, we aim to highlight X-linked NMDs including lissencephaly, periventricular nodular heterotopia and polymicrogyria because of their mostly familial inheritance pattern. We focus on the most prominent genes responsible: including DCX, ARX, FLNA, FMR1, L1CAM, SRPX2, DDX3X, NSHDL, CUL4B and OFD1, outlining what is known about their prevalence among NMDs, and the underlying pathophysiology. X-linked disorders are important to recognise clinically, as females often have milder phenotypes. Consequently, there is a greater chance they survive to reproductive age and risk passing the mutations down. Effective genetic screening is important to prevent and treat these conditions, and for this, we need to know gene mutations and have a clear understanding of the function of the genes involved. This review summarises the knowledge base and provides clear direction for future work by both scientists and clinicians alike.

Epileptic encephalopathies (EEs) are a group of heterogeneous epileptic syndromes characterized by early-onset refractory seizures, specific EEG abnormalities, developmental delay or regression and intellectual disability. The genetic spectrum of EE is very wide with mutations in a number of genes having various functions, such as those encoding AMPA ionotropic and glutamate receptors as well as voltage-gated ion channels. However, the list of EE-responsible genes could certainly be enlarged by next-generation sequencing. The present study reports a clinical investigation and a molecular analysis by the whole exome sequencing (WES) and pyrosequencing of a patient's family affected by epileptic spasms and severe psychomotor delay. Clinical and radiological investigations revealed that the patient presented clinical features of severe and drug-resistant EE-type infantile epileptic spasm syndrome that evolved to Lennox Gastaut syndrome with radiological findings of hypomyelinated leukodystrophy. The results of WES revealed the presence of a novel heterozygous c.466C>T mutation in exon 4 of the TUBB4A gene in the patient. This transition led to the replacement of arginine by cysteine at position 156 (p.R156C) of the conserved helix 4 among the N-terminal domain of the TUBB4A protein. Bioinformatic tools predicted its deleterious effects on the structural arrangement and stability of the protein. The presence of the mutation in the asymptomatic father suggested the hypothesis of somatic mosaicism that was tested by pyrosequencing of DNA from two tissues of the patient and her father. The obtained results showed a lower rate of mutated alleles in the asymptomatic father compared with the affected daughter in both lymphocytes and buccal mucosa cells, confirming the occurrence of paternal mosaicism. The phenotypic features of the patient were also compared with those of previously described patients presenting TUBB4A mutations. Our study is the first to report a disease-causing variant in the TUBB4A gene in a patient with EE associated with hypomyelinated leucodystrophy. In addition, we expanded the phenotypic spectrum associated with the TUBB4A gene.

No abstract is available for this article.