Objective: To analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children.Methods: Children hospitalized in the Department of Neurology, Hunan Children’s Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestations and imaging characteristics, five children who were only positive for GFAP-IgG antibodies in serum were excluded, and the remaining 35 children were diagnosed with autoimmune GFAP-A. The clinical data derived from the 35 children were retrospectively analyzed.Results: A total of 35 children, including 23 males and 12 females with a mean age of 6.3 ± 0.6 years, manifested clinical symptoms of fever (62.9%), headache (42.9%), convulsions (42.9%), abnormal mental behavior (51.4%), disorders of consciousness (54.3%), visual disturbance (22.9%), ataxia (11.4%), paralysis (40%), and autonomic dysfunction (25.7%). One child exhibited only the clinical symptom of peripheral facial nerve palsy. Eleven out of 35 children were also positive for other antibodies. In addition to the common overlapping autoimmune syndromes, one case of autoimmune GFAP-A also manifested as Bickerstaff’s brainstem encephalitis. Linear periventricular enhancement upon MRI was significantly less frequent in children (8.5%) than in adults. In pediatric patients, MRI contrast enhancement was principally seen in the meninges and brain lobes. Although repeated relapse (17.1%) and sequelae symptoms (20%) occurred in some cases, most children showed a favorable prognosis. Spearman’s rank correlation showed that the antibody titer was not significantly associated with the severity of the initial disease conditions.Conclusions: The disease diagnosis in children seropositive for GFAP antibodies only should receive a comprehensive diagnosis based on their clinical symptoms, imaging, electroencephalographic characteristics, and treatment responses. Some patients with relapses should receive repeated gamma globulin and corticosteroid therapy or the addition of immunosuppressants to their therapeutic regimen, and slow-dose tapering of corticosteroids and extended treatment are recommended for patients with overlapping autoimmune syndromes.

Introduction: The concurrence of intellectual disability/global developmental delay and epilepsy (ID/GDD-EP) is very common in the pediatric population. The etiologies for both conditions are complex and largely unknown. The predictors of significant copy number variations (CNVs) are known for the cases with ID/GDD, but unknown for those with exclusive ID/GDD-EP. Importantly, the known predictors are largely from the same ethnic group; hence, they lack replication. Purpose: We aimed to determine and investigate the diagnostic yield of CNV tests, new causative CNVs, and the independent predictors of significant CNVs in Chinese children with unexplained ID/GDD-EP. Materials and methods: A total of 100 pediatric patients with unexplained ID/GDD-EP and 1,000 healthy controls were recruited. The American College of Medical Genetics guideline was used to classify the CNVs. Additionally, clinical information was collected and compared between those with significant and non-significant CNVs. Results: Twenty-eight percent of the patients had significant CNVs, 16% had variants of unknown significance, and 56% had non-significant CNVs. In total, 31 CNVs were identified in 28% (28/100) of cases: 25 pathogenic and 6 likely pathogenic. Eighteen known syndromes were diagnosed in 17 cases. Thirteen rare CNVs (8 novel and 5 reported in literature) were identified, of which three spanned dosage-sensitive genes: 19q13.2 deletion (ATP1A3), Xp11.4-p11.3 deletion (CASK), and 6q25.3-q25.3 deletion (ARID1B). By comparing clinical features in patients with significant CNVs against those with non-significant CNVs, a statistically significant association was found between the presence of significant CNVs and speech and language delay for those aged above 2 years and for those with facial malformations, microcephaly, congenital heart disease, fair skin, eye malformations, and mega cisterna magna. Multivariate logistic regression analysis allowed the identification of two independent significant CNV predictors, which are eye malformations and facial malformations. Conclusion: Our study supports the performance of CNV tests in pediatric patients with unexplained ID/GDD-EP, as there is high diagnostic yield, which informs genetic counseling. It adds 13 rare CNVs (8 novel), which can be accountable for both conditions. Moreover, congenital eye and facial malformations are clinical markers that can aid clinicians to understand which patients can benefit from the CNV testing and which will not, thus helping patients to avoid unnecessary and expensive tests.

Background: The ARHGEF9 gene variants have phenotypic heterogeneity, the number of reported clinical cases are limited and the genotype–phenotype relationship is still unpredictable.Methods: Clinical data of the patients and their family members were gathered in a retrospective study. The exome sequencing that was performed on peripheral blood samples was applied for genetic analysis. We used the ARHGEF9 gene as a key word to search the PubMed database for cases of ARHGEF9 gene variants that have previously been reported and summarized the reported ARHGEF9 gene variant sites, their corresponding clinical phenotypes, and effective treatment.Results: We described five patients with developmental and epileptic encephalopathy caused by ARHGEF9 gene variants. Among them, the antiepileptic treatment of valproic acid and levetiracetam was effective in two cases individually. The exome sequencing results showed five children with point mutations in the ARHGEF9 gene: p.R365H, p.M388V, p.D213E, and p.R63H. So far, a total of 40 children with ARHGEF9 gene variants have been reported. Their main clinical phenotypes include developmental delay, epilepsy, epileptic encephalopathy, and autism spectrum disorders. The variants reported in the literature, including 22 de novo variants, nine maternal variants, and one unknown variant. There were 20 variants associated with epileptic phenotypes, of which six variants are effective for valproic acid treatment.Conclusion: The genotypes and phenotypes of ARHGEF9 gene variants represent a wide spectrum, and the clinical phenotype of epilepsy is often refractory and the prognosis is poor. The p.R365H, p.M388V, p.D213E, and p.R63H variants have not been reported in the current literature, and our study has expanded the genotype spectrum of ARHGEF9 gene. Our findings indicate that levetiracetam and valproic acid can effectively control seizures in children with epileptic phenotype caused by ARGHEF9 gene variations. These findings will help clinicians improve the level of diagnosis and treatment of the genetic disease.

This aim of this study was to analyze the correlations between clinical manifestations, treatment strategies, and the prognosis in cryptococcal meningitis (CM) in China. This was a retrospective analysis of the clinical data of CM patients treated during the years 2002-2019. The clinical features and supplementary examinations, treatment strategies, and prognosis were summarized and then a correlation analysis was performed. Fifty patients were enrolled. The most common symptoms were fever, headache, and vomiting. Five of these patients died and five had visual impairment sequelae; nine of these patients were treated before 2010. Correlation analysis suggested that cerebral hernia, consciousness disorder, visual impairment, hydrocephalus, and an intracranial pressure >300mmH2O in cerebrospinal fluid (CSF) were associated with a poor prognosis. Whether or not the application of intrathecal administration had little effect on prognosis. Early surgical intervention with internal drainage helped to reduce the mortality and incidence of visual impairment sequelae, whether or not Cryptococcus was present in the CSF before surgery. Clinically, the presence of a cerebral hernia, consciousness disorder, hydrocephalus, visual impairment, or intracranial pressure >300mmH2O often indicates a poor prognosis in patients with CM. The prognosis improved significantly after 2010, following an adjustment of the treatment strategy. Early internal drainage is the key factor, and CSF positive for Cryptococcus before surgery is not a contraindication.