Objective: There has become a consensus for detecting intellectual disability in its early stages and implementing effective intervention. However, there are many difficulties and limitations in the evaluation of intelligence-related scales in low-age children. Eye-tracking technology may effectively solve some of the pain points in the evaluation.Method: We used an eye-tracking technology for cognitive assessment. The subjects looked at a series of task pictures and short videos, the fixation points of which were recorded by the eye-movement analyzer, and the data were statistically analyzed. A total of 120 children aged between 1.5 and 4 years participated in the study, including 60 typically developing children and 60 children with global development delay, all of whom were assessed via the Bayley scale, Peabody Picture Vocabulary Test (PPVT), and Gesell scale.Results: Cognitive scores from eye-tracking technology are closely related to the scores of neuropsychological tests, which shows that the technique performs well as an early diagnostic test of children's intelligence.Conclusions: The results show that children's cognitive development can be quickly screened using eye-tracking technology and that it can track quantitative intelligence scores and sensitively detect intellectual impairment.

Objective: The dysfunction of the CLCN4 gene can lead to X-linked intellectual disability and Raynaud–Claes syndrome (MRXSRC), characterized by severe cognitive impairment and mental disorders. This study aimed to investigate the genetic defects and clinical features of Chinese children with CLCN4 variants and explore the effect of mutant ClC-4 on the protein expression level and subcellular localization through in vitro experiments.Methods: A total of 401 children with intellectual disabilities were screened for genetic variability using whole-exome sequencing (WES). Clinical data, including age, sex, perinatal conditions, and environmental exposure, were collected. Cognitive, verbal, motor, and social behavioral abilities were evaluated. Candidate variants were verified using Sanger sequencing, and their pathogenicity and conservation were analyzed using in silico prediction tools. Protein expression and localization of mutant ClC-4 were measured using Western blotting (WB) and immunofluorescence microscopy. The impact of a splice site variant was assessed with a minigene assay.Results: Exome analysis identified five rare CLCN4 variants in six unrelated patients with intellectual disabilities, including two recurrent heterozygous de novo missense variants (p.D89N and p.A555V) in three female patients, and two hemizygous missense variants (p.N141S and p.R694Q) and a splicing variant (c.1390-12T > G) that are maternally inherited in three male patients. The p.N141S variant and the splicing variant c.1390-12(T > G were novel, while p.R694Q was identified in two asymptomatic heterozygous female patients. The six children with CLCN4 variants exhibited a neurodevelopmental spectrum disease characterized by intellectual disability (ID), delayed speech, autism spectrum disorders (ASD), microcephaly, hypertonia, and abnormal imaging findings. The minigene splicing result indicated that the c.1390-12T > G did not affect the splicing of CLCN4 mRNA. In vitro experiments showed that the mutant protein level and localization of mutant protein are similar to the wild type.Conclusion: The study identified six probands with CLCN4 gene variants associated with X-linked ID. It expanded the gene and phenotype spectrum of CLCN4 variants. The bioinformatic analysis supported the pathogenicity of CLCN4 variants. However, these CLCN4 gene variants did not affect the ClC-4 expression levels and protein location, consistent with previous studies. Further investigations are necessary to investigate the pathogenetic mechanism.

Objective: The purpose of this study was to determine whether virtual reality-based sensory stimulation has the ability to improve the level of consciousness in pediatric disorders of consciousness compared with general rehabilitation.Methods: Thirty subjects were divided into a virtual reality (VR) group (n= 15) and a control group (n= 15). Subjects in the VR group received both general rehabilitation and exposure to VR videos; the control group received only general rehabilitation. The Glasgow Coma Scale (GCS), Coma Recovery Scale-Revised (CRS-R), and amplitude-integrated electroencephalogram (EEG) (aEEG) were used to measure the clinical behavioral response and neuroelectrophysiology before and after the treatment. The Glasgow Outcome Scale Extended Pediatric Revised (GOS-E Peds) was used to measure the social and personal functional ability after 3 months.Results: After 2 weeks of treatment, the CRS-R and GCS improved in both groups. However, the VR group had better results than the control group in the CRS-R (p= 0.003) and GCS (p= 0.045). There were no significant differences on aEEG in the two groups after treatment. According to the GOS-E Peds, the improvement of social and personal functional ability had no significant differences in the two groups. Additionally, there were no obvious adverse reactions in the two group during the treatment.Conclusions: This pilot study indicates potential benefit from the addition of VR to standard rehabilitation in pediatric disorders of consciousness. To further explore the efficacy of VR, a large-sample randomized controlled trial is warranted.

Background: Spastic paraplegia type 54 (SPG54) is a rare inherited autosomal recessive disorder, and a complex hereditary spastic paraplegia (HSP) caused by mutations in the phospholipase DDHD2 gene. SPG54 is characterized by early onset of spastic paraplegia, intellectual disability and dysplasia of corpus callosum.Case presentation: We report a 9 years and 5 months old Chinese girl with progressive spasm of the lower limbs, muscle weakness and intellectual disability. Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia and thinning of the corpus callosum. According to the Wechsler Intelligence Scale, her IQ is 42. By whole exome sequencing, novel compound heterozygous missense mutations in the DDHD2 gene [c.168G>C, p.(Trp56Cys) and c.1505T>C, p.(Phe502Ser)] were identified in the proband. Comparative amino acid sequence alignment across different species revealed that Trp56 and Phe502 in the DDHD2 protein were highly conserved during evolution. And multiple in silico prediction tools suggested that both mutations were deleterious.Conclusions: Our study reports a very rare case of complicated HSP caused by two novel compound heterozygous mutations in the DDHD2 gene. Our findings expand the genetic spectrum of SPG54.

Introduction: Variants in the SR-related C-terminal domain-Associated factor 4 (SCAF4) gene are linked to Fliedner-Zweier syndrome (FZS), which presents with diverse symptoms, including mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. However, there is a paucity of cases describing genotypes and clinical features.Case presentation: We present the case of a 4-year and seven-month-old Chinese boy displaying intellectual impairment, language development disorder, behavioral abnormalities, and distinct facial features. Whole exome sequencing (WES) identified a heterozygous nonsense mutation, c.1693C>T (p.Arg565*), located in exon 14 of the SCAF4 gene (NM_020706). Sanger sequencing confirmed paternal inheritance of this mutation. RNA sequencing from the patient demonstrated widespread transcriptional dysregulation, reinforcing the role of SCAF4 dysfunction in impaired transcription and neurodevelopmental disorders. This mutation is novel, not previously recorded in databases such as GnomAD or dbSNP, nor reported in existing literature.Conclusion: We reviewed the clinical features of the patients reported in the literature with mutations in SCAF4 gene and described the case of a Chinese patient with this mutation. This case underscores the critical need for continued exploration of genotype-phenotype correlations, enhancing our understanding of the diverse manifestations of Fliedner-Zweier syndrome and informing future diagnostic and therapeutic strategies.