Background A clinically important subgroup of children and adolescents with tic disorders develops persistent symptoms and functional impairment despite treatment, yet practical tools for early risk stratification in outpatient care are lacking. We aimed to develop and internally validate a pragmatic nomogram to predict treatment-refractory outcomes in pediatric tic disorders. Methods In this single-center retrospective cohort study, we included patients younger than 18 years with DSM-5 tic disorders who attended West China Second University Hospital between October 2021 and October 2023 and completed follow-up between April and August 2025. Treatment-refractory outcome at the end of follow-up was adjudicated using a prespecified framework that explicitly excluded pseudo-refractoriness. Vitamin D, the only substantially incomplete variable, was handled with multiple imputation. Predictors were selected using LASSO with 10-fold cross-validation and preference for the lambda.1se rule, followed by multivariable logistic regression with pooled estimates across imputed datasets. We assessed discrimination, calibration, internal validation, clinical utility, and prespecified sensitivity analyses. Results Among 806 participants, 82 (10.2%) met criteria for treatment-refractory outcome. Four predictors were retained in the final model: tic type, comorbidity burden, adverse pregnancy and perinatal factors, and psychosocial stressors. Concurrent mixed tics, greater comorbidity burden, adverse pregnancy and perinatal factors, and psychosocial stressors were independently associated with higher risk. The model showed good apparent discrimination (AUC 0.820), limited optimism after bootstrap correction (optimism-corrected AUC 0.802), acceptable calibration, and net benefit across clinically relevant threshold probabilities. Sensitivity analyses supported the robustness of the main findings. Conclusions This internally validated nomogram may help identify children and adolescents with tic disorders who are at increased risk of a treatment-refractory course. Beyond risk prediction, it may help child and adolescent mental health outpatient services identify patients who need earlier comorbidity-focused assessment, psychosocial intervention, family-school coordination, and intensified follow-up. External validation, recalibration, and prospective implementation studies are needed before routine use.

The risks and attributable burden of adverse birth outcomes from flooding remain unclear. Here, we analyzed a nationwide cohort of over 4.4 million mother-infant pairs in China, matching a spatiotemporal flood database with multiple buffer zones centered on maternal delivery hospitals to assess the health risks of multi-window flood exposure before and during pregnancy. We found that flood exposure during the three months preconception and the first trimester significantly increased the risks of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and term low birth weight (TLBW). Based on exposure assessment within a 3000-meter buffer, we estimate that between 2013 and 2019, first-trimester flood exposure accounted for 925,717 attributable cases of PTB (95% Uncertainty Interval [UI]: 814,446-1,035,426), with an attributable fraction (AF) of 13.56%; 418,333 cases of LBW (95% UI: 359,916-475,711; AF, 13.47%); 263,977 cases of SGA (95% UI: 101,700-424,152; AF, 2.81%); and 591,283 cases of TLBW (95% UI: 364,246-810,774; AF, 9.23%). This study quantifies a major perinatal health burden from flooding and identifies critical windows for intervention before and during early pregnancy.

BackgroundWe report a rare case of sodium valproate (VPA)-induced reversible myelodysplastic syndrome (MDS) in an Asian child with epilepsy, thus expanding the recognition of VPA-associated hematological toxicity. Although VPA has been widely used, the reversibility of MDS as a complication remains underreported, particularly in pediatric populations.Case summaryA 9-year-old boy with epilepsy developed pancytopenia (hemoglobin level: 77 g/L, platelet count: 83 × 109/L) and bone marrow-confirmed MDS after 6 months of VPA therapy. Following a reduction in VPA dose to 250 mg/day with adjunctive lacosamide, hematological parameters normalized within 3 months, and a repeat bone marrow examination revealed resolution of dysplastic features. Seizure control was maintained without relapse. This case highlights the dose-dependent nature of VPA-induced MDS and demonstrates its reversibility upon therapeutic intervention.ConclusionThe reversibility of VPA-induced MDS following dose adjustment underscores the importance of vigilant hematological monitoring in children.

BACKGROUND:To summarize and evaluate recent advances in the genetics of tic disorders (TDs) and to understand the possible pathogenic mechanisms behind this disorder. METHODS:PubMed, EMBASE, the Cochrane Library, and four Chinese databases were searched from inception to September 2022. Observational original studies that explored genetic or chromosomal variations associated with the etiology, diagnosis, treatment, or prognosis of TDs were included. The Strengthening the Reporting of Genetic Association Studies (STREGA) statement was used to evaluate the quality of the included studies. RESULTS:125 studies were finally included with 119 of moderate quality and 6 of low quality. A total of 32,439 cases with different types of TDs and 81,923 controls were included. The results involved 98 genes, 16 chromosomes, and multiple gene sets. Genome-wide studies were also included. The top three systems were the dopamine system, nervous system development, and the serotonin system. 96 loci in 56 genes and 20 regions in 14 chromosomes were reported to be relevant to TDs, with SLC6A4 (serotonin system) and NTN4 genes being relatively strongly correlated with the occurrence of TS, and ACP1 (serotonin system) and DBH (dopamine system) being relatively strongly correlated with TS comorbid with attention deficit hyperactivity disorder (ADHD). CONCLUSION:Polygenic loci were found to play a key role in the occurrence and development of TDs. However, the applicability of the findings may be limited due to the small sample size, single-center design and the limited study quality of included studies. Future research with more comprehensive study designs and improved reporting transparency is needed to confirm the findings.

Birth outcomes are linked to postnatal metabolic adaptation and long-term health, but their associations with neonatal metabolite profiles remain poorly understood. This study aimed to delineate the associations of key birth outcomes with a panel of 11 amino acids and 27 acylcarnitines in a large-scale newborn population. This cross-sectional study analyzed data from 3,398,012 neonates across 14 regions in China from April 2013 to May 2019. We compared metabolite levels between preterm and full-term infants using the Wilcoxon rank-sum test, and among low, normal, and high birth weight groups using the Kruskal–Wallis test with Dunn’s post hoc analysis. Multivariable linear regression was used to examine the associations of gestational age and sex-specific birth weight for gestational age z-scores (BWZ) with metabolite concentrations. Restricted cubic splines were employed to model potential nonlinear relationships. Pathway enrichment analysis was conducted to identify implicated metabolic pathways. Finally, we performed several sensitivity analyses to test the robustness of the findings. The cohort comprised 52.8

BackgroundArboleda-Tham syndrome (ARTHS), caused by likely pathogenic or pathogenic variants in the KAT6A gene, is characterized by developmental delay, distinctive facial dysmorphic features, and congenital cardiac anomalies. ARTHS warrants consideration in the differential diagnosis of neonates exhibiting unexplained cardiac arrhythmias, seizures, and dysmorphic features, although neonatal-onset manifestations remain underrecognized.CaseWe report two Chinese patients with KAT6A variants diagnosed in the neonatal period who presented with life-threatening manifestations. Two unrelated neonates presented with severe cardiac arrhythmias or seizures within the first month of life, in association with congenital heart defects and developmental delay. Whole-exome sequencing (WES) identified two de novo KAT6A variants: a novel splice-site variant (c.3352 + 1G>C) in patient 1, who developed supraventricular tachycardia at 23 days of life, and a previously reported missense variant (c.4645G>A; p. Gly1549Ser) in patient 2 with seizures onset at 11 days. Both patients exhibited complex congenital heart disease (Patient 1: VSD, ASD and PDA; Patient 2: PFO and PDA), developmental delay, and characteristic dysmorphic features consistent with ARTHS.ConclusionThis report highlights the critical role of genomic sequencing in the diagnostic evaluation of neonates with unexplained cardiac arrhythmias or seizures. WES should be considered in neonates exhibiting severe early-onset multisystem involvement and dysmorphic features to investigate potential KAT6A variants. These findings substantially expand the phenotypic spectrum of ARTHS by documenting severe neonatal manifestations and contribute to a deeper understanding of KAT6A-related phenotypic variability.

The gut-vascular axis has emerged as a critical focus of research, with accumulating evidence suggesting distinct alterations in intestinal microbiota among patients with Kawasaki disease (KD). However, no systematic review to date has comprehensively characterized gut microbial dysbiosis in this population. This systematic review aimed to investigate changes in the composition of gut microbiota in KD patients. A comprehensive search of MEDLINE, EMBASE, Web of Science, and the Cochrane Library databases was conducted, and the study quality was assessed using the Newcastle-Ottawa Scale. All reported taxa were re-annotated according to the SILVA 138 database. Seven studies were enrolled in our review. In acute-phase KD, reduced α-diversity and significant β-diversity divergence were observed compared to healthy controls (HCs). Concurrently, taxa with potential short-chain fatty acid (SCFA)-linked protective functions showed diminished abundance, including Bacteroidota, Bacteroides, Roseburia, Faecalibacterium, Blautia, Dialister, Lachnospira, and Prevotella, while opportunistic pathogens such as Enterococcus were enriched in acute-phase KD cohorts. For non-acute KD patients, β-diversity remained distinct, with reduced abundance of the SCFA-producing genus Blautia. These findings suggest that gut microbiota dysbiosis may be associated with KD pathogenesis via immunomodulatory pathways, although the mechanistic insights remain to be elucidated.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251148103

Parents’ beliefs and attitudes toward their children with Tourette syndrome (TS) influence treatment-seeking behaviors. This study aimed to explore and describe the Chinese parents’ perspectives on the causes of TS for their children. A qualitative study using semi-structured interviews was conducted with the parents of TS patients from a children’s hospital in western China from June to July 2021, and thematic analysis was performed to transcribe interviews and identify themes. A total of 13 participants were interviewed in this study. Five themes were developed in relation to the cognition of the causes of TS in parents, including physical problems, parenting and education problems, mental problems, bad habits, and neurological problems. Due to the insufficient awareness of TS, most parents repeatedly seek medical advice that they regarded the symptoms as physical problems or neurological problems. They generally felt guilty and blamed themselves for their parenting styles and education methods. And some parents attributed it to the poor psychological quality or the bad habits of children. Study findings showed a lack of scientific understanding of the causes of TS among parents further hindered the timely effective treatment for patients and affected the family relationships, which highlights the importance of public education and raising awareness of the disease.

Background Caregivers of pediatric patients with tic disorders (TD) are at high risk for anxiety and depression, but the situation of this disorder was rarely reported based on the Chinese population. The purpose of this study was to investigate the prevalence and potential contributing factors of anxiety and depression among caregivers of Chinese pediatric patients with TD. Methods A cross-sectional study was carried out on caregivers of pediatric patients with TD at a women’s and children’s hospital in western China from January to June 2020. A structured questionnaire was designed to collect data, including socio-demographic information, disease and medication status, family situation and social relationship, cognition and attitude towards TD and treatment. Anxiety and depression were assessed using the self-rating anxiety scale (SAS) and self-rating depression scale (SDS), respectively. The univariate analysis and multivariate logistic regression were used to analyze the cross-sectional data. Results A total of 318 participants were included in this study, with a response rate of 89.58% (318/355). The average age of pediatric patients with TD was 8.38 ± 2.54 years, and 78.30% (249/318) of caregivers were aged between 30–50 years old. Overall, 14.78% (47/318) of caregivers presented the symptom of anxiety, with a mean SAS score of 54.81±5.26, and 19.81% (63/318) of caregivers presented the symptom of depression, with a mean SDS score of 59.64±5.83. Logistic regression analysis revealed that the common family relationship (OR = 2.512, p = 0.024), and pediatric patients with unharmonious social relationships (OR = 5.759, p = 0.043) and with introverted personality (OR = 2.402, p = 0.023) were significantly associated with anxiety in caregivers of pediatric patients with TD, as well as the single-parent family (OR = 4.805, p = 0.011), mistaken cognition of TD (OR = 0.357, p = 0.031), and pediatric patients with fewer friends (OR = 3.377, p = 0.006) were significantly associated with depression. Conclusions Anxiety and depression are prevalent among caregivers of TD pediatric patients, which brings up the importance of psychiatric support for this group. Longitudinal studies need to be conducted to further confirm the causality before interventions to improve mental health are developed.

ObjectiveBiallelic variants of RARS1, a gene that encodes the cytoplasmic tRNA synthetase for arginine (ArgRS), are associated with central nervous system (CNS) manifestations, such as hypomyelinating leukodystrophy-9 and developmental and epileptic encephalopathy (DEE). This study aimed to better understand the RARS1 biallelic mutations and the associated phenotypes, particularly in patients with DEE. MethodsWe identified two patients with RARS1 biallelic mutations and functionally validated these mutations in vitro. Furthermore, we performed a review of the literature. ResultsTwo patients with hypomyelinating leukodystrophy were found to have RARS1 biallelic variants (Patient 1: c.1535G>A (p.Arg512Gln) and c.1382G>A (p.Arg461His); Patient 2: homozygous variants c.5A>T (p.Asp2Val)). Patient 2 had a severe clinical manifestation of DEE. A review of the literature identified 27 patients from five studies. Among the 29 patients, intellectual disability, developmental delay, and hypomyelination were the common symptoms, while 13 of them exhibited DEE and malformations of cortical development. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 10 patients. ArgRS protein expression and stability were substantially reduced in the two newly identified patients. SignificancePatients with RARS1 biallelic mutations frequently exhibit DEE, a severe phenotype, along with hypomyelinating leukodystrophy. Besides its effects on the white matter, this mutation also influences cortical development. Moreover, the variants c.5A>T (p.Asp2Val), c.1382G>A (p.Arg461His), and c.1535G>A (p.Arg512Gln) are pathogenic and affect the expression of ArgRS by reducing the protein stability.

Objectives: To compare the effectiveness and safety of the new antiepileptic drug, lacosamide (LCM) with Levetiracetam, for the treatment of focal epilepsy in children. Methods: This study was a cohort study. Children with focal epilepsy who received LCM or Levetiracetam treatment in West China Second Hospital of Sichuan University were recruited and followed up for 12 months. Changes in the frequency of epilepsy, 50% and 75% responder rates, and seizure freedom rates from baseline to the maintenance period and adherence score were assessed. In addition, adverse events (AEs) were recorded. Results: 92 patients completed the study, and were divided into two groups: LCM (n = 46) and Levetiracetam (n = 46). Participants were aged from 2 to 16.3 years, with a mean epilepsy duration of 2.57 years. The average maintenance dose of LCM was 5.03 ± 1.91 mg/kg/d after the titration period. There was no significant difference between the two groups in terms of the mean seizure frequency during subsequent visits at 1, 3,6, 9, 12 months. There was significant difference between the two groups in terms of the 50% responder rate at 6 months. No serious AEs were reported in both groups. The vast majority of patients had good adherence (adherence score = 4) in the LCM group. Conclusion: LCM is effective as adjunctive therapy in children with epilepsy and has good safety, tolerability and adherence. Large sample size studies with long-term follow-up are needed in the future to comprehensively evaluate the use of LCM in children. Clinical Trial Registration: [https://www.chictr.org.cn/showproj.html?proj=41041], identifier [ChiCTR1900024507].

INTRODUCTION:For improving and optimising drug use in children, we previously developed a tool (including a series of criteria for identifying potentially inappropriate prescribing in children) by literature review and the two-round Delphi technique to prevent inappropriate medication prescriptions at the prescribing stage.OBJECTIVE:To assess the prevalence of potentially inappropriate prescription (PIP) among hospitalised children and explore risk factors associated with PIP.DESIGN:A retrospective cross-sectional study.SETTING:A tertiary children's hospital in China.PARTICIPANTS:Hospitalised children with complete medical records who received drug treatment and discharged from 1 January to 31 December 2021.OUTCOME MEASURES:We evaluated the medication prescriptions by using a series of previously developed criteria for detecting the prevalence of PIP in hospitalised children and used logistic regression to explore the risk factors (including sex, age, number of drugs, number of comorbidities, days of hospitalisation and admission departments) for PIP in children.RESULTS:A total of 87 555 medication prescriptions for 16 995 hospitalised children were analysed, and 19 722 PIPs were detected. The prevalence of PIP was 22.53%, and 36.92% of the children had at least one PIP during hospitalisation. The department with the highest prevalence of PIP was the surgical department (OR 9.413; 95% CI 5.521 to 16.046), followed by the paediatric intensive care unit (PICU; OR 8.206; 95% CI 6.643 to 10.137). 'Inhaled corticosteroids for children with respiratory infections but without chronic respiratory diseases' was the most frequent PIP. Logistic regression results showed that PIP was more likely to occur in male patients (OR 1.128, 95% CI 1.059 to 1.202) and younger patients (<2 years old; OR 1.974; 95% CI 1.739 to 2.241), and in those with more comorbidities (≥11 types; OR 4.181; 95% CI 3.671 to 4.761), concomitant drugs (≥11 types; OR 22.250; 95% CI 14.468 to 34.223) or longer hospital stay (≥30 days; OR 8.130; 95% CI 6.727 to 9.827).CONCLUSIONS:Medications for long-term hospitalised young children with multiple comorbidities should be minimised and optimised, to avoid PIP, reduce adverse drug reactions and ensure children's medication safety. The surgery department and PICU had a high prevalence of PIP in the studied hospital and should be the focus of supervision and management in routine prescription review.

Objective:To explore the clinical features, lysosomal enzymatic [acid α-glucosidase (GAA)] activities and genetic variants in a child with late-onset Pompe disease (LOPD).Methods:Clinical data of a child who had presented at the Genetic Counseling Clinic of West China Second University Hospital in August 2020 was retrospectively analyzed. Blood samples were collected from the patient and her parents for the isolation of leukocytes and lymphocytes as well as DNA extraction. The activity of lysosomal enzyme GAA in leukocytes and lymphocytes was analyzed with or without addition of inhibitor of GAA isozyme. Potential variants in genes associated with neuromuscular disorders were analyzed, in addition with conservation of the variant sites and protein structure. The remaining samples from 20 individuals undergoing peripheral blood lymphocyte chromosomal karyotyping were mixed and used as the normal reference for the enzymatic activities.Results:The child, a 9-year-old female, had featured delayed language and motor development from 2 years and 11 months. Physical examination revealed unstable walking, difficulty in going upstairs and obvious scoliosis. Her serum creatine kinase was significantly increased, along with abnormal electromyography, whilst no abnormality was found by cardiac ultrasound. Genetic testing revealed that she has harbored compound heterozygous variants of the GAA gene, namely c. 1996dupG (p.A666Gfs*71) (maternal) and c. 701C>T (p.T234M) (paternal). Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 1996dupG (p.A666Gfs*71) was rated as pathogenic (PVS1+ PM2_Supporting+ PM3), whilst the c. 701C>T (p.T234M) was rated as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PM5+ PP3). The GAA in the leukocytes from the patient, her father and mother were respectively 76.1%, 91.3% and 95.6% of the normal value without the inhibitor, and 70.8%, 112.9% and 128.2% of the normal value with the inhibitor, whilst the activity of GAA in their leukocytes had decreased by 6 ~ 9 times after adding the inhibitor. GAA in lymphocytes of the patient, her father and mother were 68.3%, 59.0% and 59.5% of the normal value without the inhibitor, and 41.0%, 89.5% and 57.7% of the normal value with the inhibitor, the activity of GAA in lymphocytes has decreased by 2 ~ 5 times after adding the inhibitor. Conclusion:The child was diagnosed with LOPD due to the c. 1996dupG and c. 701C>T compound heterozygous variants of the GAA gene. The residual activity of GAA among LOPD patients can range widely and the changes may be atypical. The diagnosis of LOPD should not be based solely on the results of enzymatic activity but combined clinical manifestation, genetic testing and measurement of enzymatic activity.

BACKGROUND Perampanel (PER), a third-generation antiepileptic drug, is a selective and noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, and has been approved for the treatment of adults and adolescents with focal epilepsy. However, there are only a few studies about the efficacy and tolerability of PER in young children with multidrug-resistant epilepsy. In this case, we aimed to share our clinical experience in this group. CASE SUMMARY A 4-year-old boy without perinatal asphyxia and familial history of epilepsy began to have ictal seizures from age 14 mo, with jerky movement of four limbs and head nodding. Abnormal multifocal discharge and background activity were recorded through electroencephalography, and no pathogenic mutation was found in the whole exome sequencing for the patient and his parents. He had received valproate, levetiracetam, topiramate, oxcarbazepine, clonazepam and lacosamide sequentially at different times, but he still had frequent seizures even after vagus nerve stimulation (VNS) implantation. He was diagnosed with idiopathic multidrug-resistant epilepsy. However, his seizure frequency was significantly reduced after PER administration in a dose-dependent manner, and better cognitive behavior was observed. In addition, the adverse reactions of anger and aggression also appeared. CONCLUSION PER is effective as add-on therapy for young children with multidrug-resistant epilepsy who have previously undergone VNS implantation.

Background: More than half of adverse drug events in pediatric patients are avoidable and blocking medication errors at the prescribing stage might be one of the most effective preventive measures.Objective: To form a tool (a series of criteria) for detecting potentially inappropriate prescriptions in children, promote clinical rational drug use and reduce risks of medication in children.Methods: Potentially inappropriate prescription propositions for children were collected through a systematic review. Then, the Delphi technique was adopted to form the final criteria. Panelists were asked to use a 5-point Likert scale to rate their agreement with each potentially inappropriate prescription proposition and were encouraged to add new propositions based on their clinical experience and knowledge. After 2 rounds of Delphi survey and propositions were fully revised and improved, the final criteria for identifying potentially inappropriate prescriptions in children were formed.Results: The final criteria for identifying potential inappropriate prescriptions in children has 136 propositions, which were divided into “criteria for children with non-specific diseases/conditions” (71 propositions: 68 for potentially inappropriate medication, 3 for potential prescribing omission) and “criteria for children with specific diseases/conditions” (65 propositions: 55 for potentially inappropriate medication, 10 for potential prescribing omission), according to whether the proposition was about identifying specific risks associated with one drug in children with a specific other diseases/conditions that do not exist in children with other diseases/conditions.Conclusion: A tool for screening potentially inappropriate prescriptions in children is formed to detect potentially inappropriate medication and prescribing omission in pediatrics and is available to all medical professionals liable to prescribe or dispense medicines to children.

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive carbohydrate metabolism disorder. The main symptoms of FBS are hepatomegaly, nephropathy, postprandial hyperglycemia, fasting hypoglycemia, and growth retardation. Hypokalemia is a rare clinical feature in patients with FBS. In this study, we present a neonate suffering from FBS. She presented with hypokalemia, dysglycaemia, glycosuria, hepatomegaly, abnormality of liver function, and brain MRI. Trio whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants. A compound heterozygous mutation (NM_000340.2; p. Trp420*) of SLC2A2 was identified. Here, we report a patient with FBS in a consanguineous family with diabetes, severe hypokalemia, and other typical FBS symptoms. Patients with common clinical features may be difficult to diagnose just by phenotypes in the early stage of life, but WES could be an important tool. We also discuss the use of insulin in patients with FBS and highlight the importance of a continuous glucose monitoring system (CGMS), not only in diagnosis but also to avoid hypoglycemic events.

Abstract Background The diagnosis of epilepsy in a child often and understandably causes psychological adjustment difficulties in the parents. To help parents of children with epilepsy cope with stress, it is important to understand how parents cope with the sickness of their child. The objective of this study was to assess factors related to the state of anxiety and depression among parents of children with epilepsy. Methods The present study was a cross‐sectional study, and the data were collected through an anonymous, Internet‐based survey platform between October 2018 and October 2019 from 250 participants aged 22–65 years. Participants were invited to fill questionnaires include socioeconomic questionnaire, anxiety, depression, and coping strategies scale. Result Among the parents of children with epilepsy, 48.8% (122/250) had depressive symptoms (Patient Health Questionnaire‐9 [PHQ‐9] score >4) and 46.4% (116/250) had anxiety symptoms (7‐item Generalized Anxiety Disorder [GAD‐7] score >5). Depression among parents of children with epilepsy was significantly associated with comorbidity (odds ratio [OR] = 0.392, 95% CI = 0.182–0.846), a poor parental relationship (OR = 0.283, 95% CI = 0.130–0.614), positive coping (OR = 0.947, 95% CI = 0.903–0.992), and negative coping (OR = 1.287, 95% CI = 1.179–1.405). Anxiety among parents of children with epilepsy was significantly associated with a poor parental relationship (OR = 0.416, 95% CI = 0.207–0.835) and negative coping (OR = 1.155, 95% CI = 1.087–1.228). Conclusions The present study indicates the importance of couple support and providing effective coping to make parents of children with epilepsy more resilient in the presence of negative life events, especially for parents of children with comorbidity with cognitive deficiency.

Objective:KCNT2 gene mutations had been described to cause developmental and epileptic encephalopathies (DEEs). In this study, we presented the detailed clinical features and genetic analysis of two unrelated patients carrying two de novo variants in KCNT2 and reviewed eight different cases available in publications.Methods: Likely pathogenic variants were identified by whole exome sequencing; clinical data of the patients were retrospectively collected and analyzed.Results: Our two unrelated patients were diagnosed with Ohtahara syndrome followed by infantile spasms (IS) and possibly the epilepsy of infancy with migrating focal seizures (EIMFS), respectively. They both manifested dysmorphic features with hirsute arms, thick hair, prominent eyebrows, long and thick eyelashes, a broad nasal tip, and short and smooth philtrum. In the eight patients reported previously, two was diagnosed with IS carrying a ‘change-of-function' mutation and a gain-of-function mutation, respectively, two with EIMFS-like carrying a gain-of-function mutation and a loss-of-function mutation, respectively, one with EIMFS carrying a loss-of-function mutation, three with DEE without functional analysis. Among them, two patients with gain-of-function mutations both exhibited dysmorphic features and presented epilepsy phenotype, which was similar to our patients.Conclusion: Overall, the most common phenotypes associated with KCNT2 mutation were IS and EIMFS. Epilepsy phenotype associated with gain- and loss-of-function mutations could overlap. Additional KCNT2 cases will help to make genotype-phenotype correlations clearer.

Dear Dr. Lian-Sheng Ma and editorial office: Please find attached revised version of our manuscript (No. 70630), entitled “Young children with multidrug-resistant epilepsy and vagus nerve stimulation responding to perampanel: a case report and literature review”, which we resubmit again for publication as a case report in World Journal of Clinical Cases. We thank you and the reviewers for your insightful comments and patience to help us improving the quality of our work. Accordingly, we have carefully checked and revised this manuscript again, and added some discussion and references. And our point-by-point responses to each of the reviewers’ comments are presented below. We hope that our manuscript is now acceptable for publication in the journal. On behalf of the co-authors, I am looking forward to your favorable decision. Thank you very much for your kind consideration.