Objective: The aim of this study was to analyze the phenotypic spectrum, treatment, and prognosis of 72 Chinese children with SCN2A variants.Methods: The SCN2A variants were detected by next-generation sequencing. All patients were followed up at a pediatric neurology clinic in our hospital or by telephone.Results: In 72 patients with SCN2A variants, the seizure onset age ranged from the first day of life to 2 years and 6 months. The epilepsy phenotypes included febrile seizures (plus) (n = 2), benign (familial) infantile epilepsy (n = 9), benign familial neonatal-infantile epilepsy (n = 3), benign neonatal epilepsy (n = 1), West syndrome (n = 16), Ohtahara syndrome (n = 15), epilepsy of infancy with migrating focal seizures (n = 2), Dravet syndrome (n = 1), early infantile epileptic encephalopathy (n = 15), and unclassifiable developmental and epileptic encephalopathy (n = 8). Approximately 79.2% (57/72) patients had varying degrees of developmental delay. All patients had abnormal MRI findings with developmental delay. 91.7% (55/60) patients with de novo SCN2A variants had development delay, while only 16.7% (2/12) patients with inherited SCN2A variants had abnormal development. 83.9% (26/31) SCN2A variants that were located in transmembrane regions of the protein were detected in patients with development delay. Approximately 69.2% (9/13) SCN2A variants detected in patients with normal development were located in the non-transmembrane regions. Approximately 54.2% (39/72) patients were seizure-free at a median age of 8 months. Oxcarbazepine has been used by 38 patients, and seizure-free was observed in 11 of them (11/38, 28.9%), while 6 patients had seizure worsening by oxcarbazepine. All 3 patients used oxcarbazepine and with seizure onset age > 1 year presented seizure exacerbation after taking oxcarbazepine. Valproate has been used by 53 patients, seizure-free was observed in 22.6% (12/53) of them.Conclusion: The phenotypic spectrum of SCN2A-related epilepsy was broad, ranging from benign epilepsy in neonate and infancy to severe epileptic encephalopathy. Oxcarbazepine and valproate were the most effective drugs in epilepsy patients with SCN2A variants. Sodium channel blockers often worsen seizures in patients with seizure onset beyond 1 year of age. Abnormal brain MRI findings and de novo variations were often related to poor prognosis. Most SCN2A variants located in transmembrane regions were related to patients with developmental delay.

Objective: Epilepsy is a chronic disease that places a heavy burden on caregivers. Previous studies have shown that caregivers of epilepsy patients often experience anxiety and depression; however, few comprehensive studies have assessed their sleep quality and family function. Based on the current understanding of the anxiety and depression state of caregivers in children with epilepsy, we further explored the caregivers' sleep and family function and evaluated the predictors of the depression state of caregivers.Methods: In this cross-sectional online anonymous survey, we sent an online questionnaire to the caregivers of children with epilepsy who visited our hospital. The QR code of the questionnaire was scanned at the follow-up course to conduct an online survey. The questionnaire contained questions about sociodemographic and clinical information, the Self-rating Anxiety Scale, Self-rating Depression Scale, Pittsburgh Sleep Quality Index, and the Family Assessment Device.Results: A total of 308 caregivers of children with epilepsy aged 0–12 years were included in this study. The mean age of children with epilepsy was 4.8 ± 3.18 years, and the average illness duration was 34.2 ± 29.18 months. Further, 47.1% of the children took three or more anti-seizure medications, and 43.2% were on ketogenic diet therapy. We found that in 77.9% of the cases, the subjects were the mothers, in 89% there was more than one co-caregiver, and in 51.9%, financial help was required. Further, 63.6% of the caregivers thought they could not get enough access to disease knowledge education, and 83.7% perceived epilepsy was a terrible disease. Our results also showed that 65.6% of the caregivers were in depression status, 41.9% were in anxiety status, and 49.0% had poor sleep quality. The proportion of unhealthy family functioning in each subscale was 45.1–96.1%, and the unhealthy behavior control function accounted for 96.1%. Binary logistic regression analysis of the data showed that without co-caregivers [odds ratio (OR), 5.193], free of anxiety status (OR, 0.063), good sleep quality (OR, 0.446), healthy family role dimension (OR, 0.344), and healthy family general functional dimension (OR, 0.259) were predictors of depression status in caregivers of children with epilepsy.Conclusion: Anxiety and depression status are common in caregivers of children with epilepsy, with depression status being more prominent. Moreover, a considerable proportion of caregivers had poor sleep quality and unhealthy family function. The caregivers' anxiety status, sleep quality, family role dimension, family general function dimension, and the number of co-caregivers were predictors of depression status in caregivers. In clinical practice, caregivers' anxiety and depression status, poor sleep quality, and unhealthy family functioning should be addressed along with the treatment of children with epilepsy.

Purpose: This study was designed to assess the effects of epilepsy severity, family resilience, and social support on depression in primary caregivers of children with epilepsy (CWE), and to test the mediating roles of family resilience and social support in this relationship.Method: Two hundred fifty-two caregivers of children with epilepsy were recruited from October 2020 to May 2021. The questionnaire contained sociodemographic characteristics, Epilepsy Severity, Chinese-Family Resilience Assessment Scale (C-FRAS), Social Support Rating Scale (SSRS), Beck Depression Inventory (BDI). Structural equation models were used to evaluate whether family resilience and social support as mediators between epilepsy severity and depression.Results: In this study, the prevalence of depressive symptoms among primary caregivers of CWE in China was 69.84%. Epilepsy severity was positively associated with depression. Family resilience and social support were negatively correlated with depressive symptoms (both p < 0.01). Furthermore, the fitness indices of structural models were satisfactory. The direct effect of epilepsy severity on depression was 0.266 (95% CI 0.064–0.458), this pathway explained 62.88% variance of depression. The indirect effect of family resilience and then social support was 0.069 (95% CI 0.025–0.176), indicating that the serial multiple mediation was significant. The serial mediation pathway explained 16.31% variance of depression.Conclusions: The high incidence of depression among primary carers of CWE deserves more attention. They should be screened routinely, especially those parents of children with severe epilepsy. Family resilience and social support could be protective factors for caregivers' mental adjustment. Therefore, future psychosocial interventions for enhancing family resilience and social support should be implemented, in order to reduce their depression.

Objective: We aimed to explore the associated clinical phenotype and the natural history of patients with SYNGAP1 gene variations during early childhood and to identify their genotype–phenotype correlations.Methods: This study used a cohort of 13 patients with epilepsy and developmental disorder due to SYNGAP1 mutations, namely, 7 patients from Shenzhen Children’s Hospital between September 2014 and January 2020 and 6 patients from previously published studies. Their clinical data were studied.Results: A total of 13 children with SYNGAP1 gene variants (eight boys and five girls) were identified. The age of disease onset was in infancy. Mutations were located between exons 8 and 15; most were frameshift or truncated mutations. Four mutation sites (c.924G > A, c.1532-2_1532del, c.1747_1755dup, and c.1735_1738del) had not been reported before. All patients had global developmental delay within the first year of life, and intellectual impairment became gradually apparent. Some of them developed behavioral problems. The developmental delay occurred before the onset of seizures. All seven patients in our cohort presented with epilepsy; myoclonic seizures, absence seizures, and epileptic spasms were the most common seizure types. Abnormal electroencephalograms were identified from five patients before the onset of their seizures. All patients suffered from drug-resistance seizures. However, comorbidities such as behavioral problems were less frequently observed.Conclusion: The most common age of disease onset in SYNGAP1 gene mutations is in infancy, while neurodevelopmental delay and epilepsy are the major phenotypes. They have a higher percentage of drug-resistant epilepsy and epileptic spasms than those in previous reports. We should give attention to the patients with abnormal EEGs without seizures and think about the suitable time of the anti-seizure medications for them. We have not found the genotype–phenotype correlation.Trial registration: Chinese Clinical Trial Registry, Registration number: ChiCTR2100049289 (https://www.chictr.org.cn/listbycreater.aspx).