Objective To analyze the clinical and genetic variation characteristics of hereditary epilepsy in neonates and explore the correlation between the characteristics of genetic variations and clinical manifestations. Methods A retrospective collection was made of neonatal hereditary epilepsy cases admitted to Hebei Children's Hospital from January 2019 to December 2024. The cases were divided into KCNQ2 group and non-KCNQ2 group based on the results of gene sequencing. The clinical features of the two groups were compared, and the genotype-phenotype correlation of KCNQ2 was analyzed. Results A total of 43 cases of neonatal hereditary epilepsy were included, including 26 boys and 17 girls, with a gestational age of 39.4 (38.1-40.3) weeks and a birth weight of 3400 (3000-3400) g. There were 24 cases in the KCNQ2 group and 19 cases in the non-KCNQ2 group. The onset time of epilepsy was 3.0 (2.0-7.0) days after birth, which was earlier in the KCNQ2 group than in the non-KCNQ2 group (P<0.05). The main seizure forms were clonic (62.8%) and tonic (53.5%) seizures. The main abnormality on head MRI was abnormal brain parenchymal signal (72.1%). The most common finding on video electroencephalogram was multifocal discharges (34.9%). There were no statistically significant differences between the two groups (P>0.05). In the KCNQ2 group, there were 13 cases of self-limiting neonatal epilepsy (SeLNE) and 11 cases of developmental and epileptic encephalopathy (DEE). Among the 23 cases successfully followed up, 19 cases had seizure control, 8 cases had significant developmental delay, and 2 cases died. In the non-KCNQ2 group, there was 1 case of SeLNE, 10 cases of DEE, and 8 other cases. Among the 13 cases successfully followed up, 7 cases had seizure control, 7 cases had significant developmental delay, and 4 cases died. The proportion of SeLNE in the KCNQ2 group was higher than that in the non-KCNQ2 group (54.2% vs. 5.3%, P<0.01), and the proportion of death and significant developmental delay was lower in the KCNQ2 group (43.5% vs. 84.6%, P=0.033). There were 19 cases of KCNQ2 nucleotide sequence variations, including 10 cases of SeLNE, 5 cases of hereditary variations, and 4 cases of missense variations. Seven amino acid changes were located at the C-terminal. All 9 cases of DEE were de novo variations, including 7 cases of missense variations, and 5 amino acid changes were located at the S4, S6 and adjacent regions, and the B-helix region. Prediction of protein structural changes induced by 11 missense variants: among 4 SeLNE cases, 2 showed alterations in protein secondary structure, 3 exhibited changes in hydrogen bonds, and 4 demonstrated decreased protein stability; among 7 DEE cases, 6 displayed alterations in protein secondary structure, 4 presented changes in hydrogen bonds, and 6 manifested decreased protein stability. Conclusions KCNQ2 gene variations are the most common in neonatal hereditary epilepsy. Compared with other gene variations, KCNQ2-induced neonatal epilepsy has an earlier onset time and a lower proportion of adverse outcomes. Among them, de novo, missense, and variations at important functional domain sites, may be associated with severe phenotypes of DEE.

Objective To report and analyze the clinical phenotypes and genotypes of two cases of spinal muscular atrophy (SMA) caused by structural variations in exon 1 of the survival motor neuron 1 (SMN1) gene. Methods A retrospective analysis was conducted on the clinical data of two children with SMA caused by structural variations in exon 1 who visited the neurology department from October 2022 to June 2024. Peripheral blood samples were collected from the patients and their parents. Diagnosis of 5q SMA was ultimately confirmed using long-range PCR (LR-PCR) combined with multiplex ligation-dependent probe amplification (MLPA) kit P021. A literature review of SMA cases associated with exon 1 variations in SMN1 gene was also conducted. Results Both of the two children with SMA caused by structural variations in exon 1 were male, type Ⅱ. Their ages of onset were 7 months and 9 months respectively, and their ages of seeking medical attention were 9 years and 1 month and 1 year and 1 month respectively. They all presented with limb muscle weakness and delayed motor development, and electromyography all indicated lesions in the anterior horn of the spinal cord. Routine MLPA testing initially identified heterozygous deletion of the SMN1 gene in both patients. Definitive diagnosis via LR-PCR combined with MLPA-P021 revealed an SMN1 exon 7 copy number of 1 on one allele, coupled with a structural deletion variant in exon 1 on the same allele. Additionally, Patient 1 harbored an SMN1/SMN2 hybrid gene on this allele. The extended diagnostic interval of 11 years for Patient 1 was attributed to both the earlier time of birth and the rarity of the combined gene conversion and structural variation. Literature review identified 7 relevant publications reporting 19 SMA cases (male-to-female ratio 12∶7) caused by exon 1 variations, including missense, nonsense, and structural deletion variants. Age of onset ranged from birth to adolescence, with primary manifestations being motor function delay or regression. Five patients were deceased; some receiving SMA-targeted therapies were reported to be stable. Conclusions Both SMA cases in this study were caused by structural variations in exon 1 of the SMN1 gene, confirming 5q SMA. When initial MLPA testing in clinically suspected SMA patients is negative (i.e., no homozygous deletion of exon 7 is detected), variations in exon 1 should be considered. The optimized LR-PCR combined with MLPA-P021 technique enables rapid and precise diagnosis. Exon 1 may represent a hotspot in the Chinese SMA variant spectrum, and gene conversion events warrant particular attention.

Objective To investigate the clinical manifestations and genetic characteristics of 2 patients with intellectual disability, X-linked, syndromic, Bain type (MRXSB). Methods Two female children who visited the hospital due to "global growth and development delay and intellectual disability" in January 2023 and November 2023 were taken as the research subjects, and the clinical data of the probands were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing verification were performed on the proband and his family. The methylation-sensitive sites were analyzed by using the XCI detection kit (XCI Filer), and the degree of X chromosome bias inactivation was quantitatively analyzed in combination with capillary electrophoresis. Bioinformatics tools were used to predict the pathogenicity of variations. Results The two children were girls aged 11 and 10 months respectively, both presenting with global growth and development delay, intellectual disability, hypotonia and absence of motor milestones. Among them, proband 1 was accompanied by feeding difficulties, dysphagia and shortness of breath symptoms. The results of trio-WES indicated that both of the two children had heterozygous variations of c.616C>T(p.Arg206Trp) in the HNRNPH2 gene (NM_019597), and Sanger sequencing verification suggested that the variations were all spontaneous variations. XCI analysis indicated that both of the two children had X chromosome bias inactivation, with bias rates of 17.3% and 14.0% respectively. Conclusions This study diagnosed for the first time two girls with MRXSB whose age of onset was<1 year old. Through XCI analysis, it was found that the X chromosomes of all the children were inactivated due to bias. Combined with the earlier and more typical clinical phenotypes of the patients, it was speculated that the degree of XCI bias in all the children might be correlated with the severity of the phenotype. XCI is the core regulatory mechanism of clinical heterogeneity in female XLID. The combination of XCI and trio-WES is of great value for the early diagnosis and prognosis evaluation of female XLID.

Objective To summarize and analyze the clinical and pathological characteristics and short-term outcomes of eight children diagnosed with concomitant IgA nephropathy (IgAN) and membranous nephropathy (MN). Methods This retrospective case series included eight pediatric patients with biopsy-proven IgAN+MN between January 2014 and December 2024. Clinical manifestations, laboratory findings, and renal histopathology were reviewed and summarized, and the results were compared with those reported in the literature. Results The cohort comprised eight children (4 boys and 4 girls), with a median age at onset of 7 years. The main clinical presentations were gross hematuria and/or proteinuria. Nephrotic syndrome occurred in 50% of patients, and hematuria was observed in 87.5%. Renal pathology predominantly demonstrated mesangial proliferative glomerulonephritis accompanied by early- to intermediate-stage membranous lesions. Immunofluorescence showed IgA deposition in the mesangium and IgG deposition along the glomerular basement membrane. All patients were treated with glucocorticoids in combination with immunosuppressive agents. Complete remission was achieved in all cases (100%), with a median time to remission of 2 months (range, 1-5 months). Conclusion Pediatric IgAN+MN shows overlapping clinical phenotypes of IgAN and MN. Treatment with glucocorticoids plus immunosuppressants appears to be highly effective, and short-term prognosis is favorable. Early diagnosis and active intervention may improve outcomes; however, long-term follow-up is needed to monitor relapse and chronic progression.

Objective This study aimed to analyze the clinical manifestations, coronary artery lesion (CAL) features, and independent risk factors/predictive indicators for intravenous immunoglobulin (IVIg) non-response in infants with Kawasaki disease (KD) under 6 months of age. Methods A retrospective analysis was performed on clinical data of 435 KD infants aged 0-12 months who were hospitalized January 2020 to December 2024. Patients were stratified into the 0-5 months group (under 6 months) and 6-12 months group; the 0-5 months group was further subdivided into incomplete KD (iKD) and complete KD (cKD) subgroups. Differences in core clinical characteristics between the 0-5 months and 6-12 months groups were analyzed, and phenotypic variations between the iKD and cKD subgroups were compared. Multivariate logistic regression was used to identify risk factors for CAL and IVIg non-response in the 0-5 months group. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy of candidate variables for IVIg non-response. Results A total of 179 patients (41.1%) were included in the 0-5 month group. Compared with the 6-12 months group, the 0-5 months group exhibited a significantly higher incidence of Bacille Calmette-Guérin (BCG) scar erythema/swelling and elevated inflammation-related markers such as platelet count, alongside lower frequencies of typical KD symptoms like conjunctival hyperemia and reduced albumin/hemoglobin levels. The incidence of CAL was also higher in the 0-5 months group (47.5%; all P<0.05). Within the 0-5 months group, 73 patients (40.8%) were diagnosed with iKD, presenting fewer typical symptoms, a higher CAL incidence (58.9%), and a higher IVIg non-response rate than the cKD subgroup (all P < 0.05). Multivariate regression revealed that BCG scar erythema/swelling was independently associated with an increased risk of CAL (OR=2.81, 95% CI: 1.44-5.48, P=0.002). Conjunctival hyperemia was inversely correlated with IVIg non-response (OR=0.15, 95% CI: 0.03-0.89, P=0.036), while a neutrophil-to-lymphocyte ratio (NLR)≥3.78 (OR=3.17, 95% CI: 1.37-7.31, P=0.007) and fever duration≥6.5 days (OR=1.38, 95% CI: 1.03-1.84, P=0.029) were identified as independent risk factors for IVIg non-response. The combined model of NLR≥3.78 and fever duration≥6.5 days yielded an area under the ROC curve (AUC) of 0.888 for predicting IVIg non-response, with a sensitivity of 0.867 and specificity of 0.841. Conclusions KD infants under 6 months of age often present with atypical manifestations. iKD in this age group is associated with a higher incidence of CAL and IVIg non-response. BCG scar erythema/swelling is closely linked to CAL development. The combination of NLR≥3.78 and fever duration≥6.5 days has robust predictive value for IVIg non-response, while conjunctival hyperemia may facilitate the early identification and management of IVIg-nonresponsive KD in infants under 6 months.

Objective To investigate the clinical features, therapeutic strategies, and prognostic outcomes of hepatic hemangioma with arteriovenous fistula (HH-AVF) in neonates. Methods Clinical data of 8 neonates diagnosed with HH-AVF and admitted to our institution between January 2018 and December 2024 were retrospectively collected. Their clinical manifestations were analyzed, with the efficacy of interventional therapy evaluated. Results Among the 8 neonates with HH-AVF (5 males and 3 females), all presented with hepatic space-occupying lesions. Six cases developed respiratory distress requiring mechanical ventilation, with chest radiography revealing cardiomegaly and complications including heart failure and pulmonary hypertension. Two cases had multiple cutaneous hemangiomas, and one case had a cervical hemangioma with bleeding. All 8 neonates underwent interventional therapy at a median age of (29.5±9.5) days, combined with oral propranolol. One neonate showed an increase in hepatic mass on follow-up ultrasound at 4 months post-operation, prompting a second interventional embolization due to suspected tumor progression; the remaining 7 cases improved and were discharged. During a follow-up period of 12-24 months, none of the patients experienced recurrence of respiratory distress, pulmonary hypertension, or heart failure, and all lesions were significantly reduced or resolved compared to the time of diagnosis. Conclusions Neonatal-onset HH-AVF exhibits diverse clinical manifestations, with higher mortality rates in cases complicated by heart failure and pulmonary hypertension. Interventional therapy may be an effective approach to improve the prognosis of HH-AVF.

Objective To screen key phosphorylated proteins involved in vascular remodeling of aortic coarctation (CoA) using phosphoproteomics and to investigate the role of the Golgi protein GORASP1 in its pathogenesis. Methods Paired tissue samples from CoA stenotic segments and control aortic tissues (n=5 pairs) were collected. Differentially phosphorylated proteins were identified through phosphoproteomic profiling. Bioinformatics analyses were performed to elucidate the functions of these proteins and delineate the mechanism by which GORASP1 contributes to CoA. Results Functional analysis of the differential proteins between the CoA and control groups revealed significant enrichment in pathways such as oxidative stress and energy metabolism, suggesting these biological processes play important roles in CoA pathology. Notably, GORASP1 was identified as the most significantly differentially phosphorylated protein. Its functions were primarily associated with Golgi organization and the autophagy pathway, suggesting that GORASP1 may act as a key nodal molecule linking these common pathological processes to organelle dysfunction. Conclusion The specific phosphorylation signature in CoA is closely related to oxidative stress. GORASP1 likely participates in vascular remodeling by regulating organelle function and autophagy processes, providing new directions for mechanistic research and therapeutic target development in CoA.

Objective To investigate the clinical features, treatment and prognosis of pediatric ANCA-associated vasculitis (AAV) presenting initially with diffuse alveolar hemorrhage syndrome (DAHS). Methods A retrospective analysis was conducted on the clinical data of 6 children, admitted to the hospital from January 2010 to December 2023, who presented with DAHS as the initial manifestation and were eventually diagnosed with AAV. Results Among the 6 children, 4 were female and 2 were male. The median age at DAHS onset was 5.4 ( 4-7.6) years, while the median age at AAV diagnosis was 7.2 (6.3-10.6) years. The interval between DAHS onset and AAV diagnosis ranged from 6 months to 3 years. At the initial diagnosis of DAHS, ANCA testing was negative in all 6 children. All children exhibited varying degrees of anemia and were diagnosed as MPO/p-ANCA-positive microscopic polyangiitis (MPA). Chest imaging primarily showed diffuse pulmonary infiltrations, manifesting as patchy, flocculent, and ground-glass opacities. Hemosiderin-laden macrophages were found in sputum, gastric fluid, bronchoalveolar lavage fluid, or lung biopsy specimens. All 6 children had varying degrees of renal involvement. Treatment for all patients involved glucocorticoids combined with immunosuppressants or biologics. Two children underwent plasma exchange, and one received peritoneal dialysis. During a follow-up period of 24 to 84 months, pulmonary lesions in all 6 children showed significant absorption and reduction compared to previous imaging. No recurrence of hemoptysis or blood-streaked sputum was observed, and symptoms markedly improved. One patient progressed to chronic kidney disease stage 5, receiving regular peritoneal dialysis with stable condition. Conclusions DAHS is a severe complication of AAV. When presenting as the initial manifestation, DAHS may lack other characteristic features of AAV, leading to diagnostic challenges. Clinicians should maintain a high index of suspicion for such presentations. Early definitive diagnosis and aggressive treatment with glucocorticoids combined with immunosuppressants or biologics can effectively improve prognosis.

Objective To summarize the diagnosis and treatment process of a pediatric patient with rare TTMV::RARA fusion gene-positive acute promyelocytic leukemia (APL), and to explore the disease's clinical characteristics, treatment, and prognosis. Methods A retrospective analysis was conducted on the clinical data of a child with TTMV::RARA fusion gene-positive APL admitted in January 2024, and the relevant literature was reviewed. Results The patient, a 13-year-old girl, initially presented with abnormal hematopoiesis (white blood cell count 20.29×10⁹/L, hemoglobin 76 g/L, platelet count 76×10⁹/L) and bone pain. A diagnosis of APL with TTMV::RARA fusion positivity accompanied by an SF3B1 mutation was confirmed via MICM (Morphology, Immunology, Cytogenetics, Molecular biology) classification. The patient received personalized intensive therapy, which consisted of induction with all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO), along with intensified chemotherapy including cytarabine (Ara-C) and mitoxantrone (MTZ). Subsequently, autologous peripheral blood hematopoietic stem cell transplantation (APBSCT) was performed during consolidation chemotherapy, and multiple cycles of maintenance treatment were received after the transplantation. As of July 2025 (11 months post-transplant), the patient remains in sustained molecular remission (TTMV::RARA digital PCR-negative), with a disease-free survival (DFS) of 14 months. This article includes 9 cases from literature reports and 1 case from the current study, totaling 10 cases. There were 5 boys and 5 girls, with a median age of 7.5 (2 to 17) years. These children showed initial sensitivity to the treatment regimen of ATRA combined with ATO. The outcomes of the 10 pediatric patients were as follows: The patient did not undergo transplantation, remained in remission for 6 months after chemotherapy, but subsequently experienced two relapses and ultimately succumbed to disease progression; one patient underwent APBSCT during the first complete remission (CR1) and remained in continuous remission; four patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving CR1, among whom two remained in continuous remission, one experienced relapse, and one died (due to non-relapse causes); four patients received allo-HSCT during the second complete remission (CR2) after relapse, among whom two remained in continuous remission, one experienced relapse, and one died. Conclusions For patients with morphologically consistent APL who test negative for both PML::RARA and its variant fusions, rare fusion genes such as TTMV should be screened as early as possible using techniques like transcriptome sequencing (RNA-seq). TTMV::RARA fusion gene positive APL usually indicates a poor prognosis. It is recommended to use ATRA+ATO combined intensive chemotherapy and perform allo-HSCT as soon as possible. For those who do not have the conditions, APBSCT can be considered to achieve deep and sustained remission.

Porphyromonas endodontalis is a Gram-negative anaerobic bacterium commonly found in the normal oral flora and is primarily associated with odontogenic infections. Intracranial infections caused by this bacterium are extremely rare. In January 2023, a 10-year-old male was admitted to hospital due to recurrent high fever accompanied by facial swelling for 3 days and one episode of convulsion. Physical examination revealed drowsiness, swelling of the face and neck, and a positive Brudzinski's sign. Laboratory tests showed a white blood cell count of 26.16×10⁹/L, C-reactive protein of 279.57 mg/L, and procalcitonin >100 ng/mL. Cerebrospinal fluid analysis indicated a white blood cell count of 45×10⁹/L and a protein level of 945 mg/L. Head magnetic resonance imaging revealed the formation of bilateral frontal lobe abscesses. Metagenomic next-generation sequencing of blood, cerebrospinal fluid, and pus detected sequences of Porphyromonas endodontalis and various other anaerobic bacteria. A definitive diagnosis of a brain abscess caused by Porphyromonas endodontalis was established. Although initial antimicrobial therapy with vancomycin, meropenem, linezolid, and metronidazole led to transient clinical improvement, the patient experienced recurrent fever, and follow-up imaging showed abscess enlargement with a midline shift. Subsequently, surgical debridement of the subdural and epidural abscesses was performed on the 14th hospital day. Postoperative anti-infective therapy was continued for 6 weeks, resulting in the resolution of fever, absorption of the abscess, and eventual recovery upon discharge.

A retrospective analysis of the clinical manifestations, laboratory indicators, endoscopic pathology, and lymphoscintigraphy characteristics of a 5-year-7-month-old child with Primary Intestinal Lymphangiectasia (PIL) was conducted, along with a follow-up of treatment outcomes. The child presented with symptoms of diarrhea, abdominal bloating, and tetany in hands and feet. Laboratory tests revealed severe hypoalbuminemia (16.4 g·L^-1), low IgG (2.32 g·L^-1), lymphocytopenia (0.82×10⁹/L), and hypocalcemia with hypomagnesemia. Imaging studies indicated multiple serous effusions, and gastrointestinal endoscopy showed diffuse white, snowflake-like substances on the mucosa of the duodenum and terminal ileum. Pathology demonstrated lymphatic dilation with inflammatory cell infiltration. Characteristic findings from ⁹⁹Tc^m-DX lymphoscintigraphy indicated persistent imaging of the left venous angle, suggesting obstruction at the thoracic duct outlet. Treatment with a low-fat, high-protein, high-medium-chain triglyceride (MCT) diet combined with albumin infusion led to a significant increase in albumin levels to 26.8 g·L^-1 after 7 days, with a marked alleviation of symptoms. The main clinical manifestations of primary intestinal lymphangiectasia in children include diarrhea, abdominal bloating, edema, hypoproteinemia, and electrolyte disturbances. Lymphoscintigraphy confirmed the key pathological mechanism of thoracic duct obstruction, providing a reliable imaging basis for the etiological diagnosis of the disease.

As a conditional pathogenic fungus, invasive or disseminated Trichosporon asahii infection mostly occurs in immunodeficient patients, and cases involving the digestive system are relatively rare. This paper reports a rare case of disseminated Trichosporon asahii infection in a child without underlying diseases, mainly involving the gastrointestinal tract, liver and gallbladder, and abdominal lymph nodes. In October 2023, a 7-year-and-6-month-old male child was admitted to our hospital with "abdominal pain for 5 months, anemia accompanied by intermittent fever for more than 3 months". The main clinical manifestations were abdominal pain, anemia, and recurrent fever. Imaging, endoscopic, and pathological examinations indicated that the infection involved the liver and gallbladder, stomach, duodenum, and mesenteric lymph nodes. Multiple antifungal therapies were ineffective. Ultimately, Trichosporon asahii infection was confirmed by next-generation sequencing (NGS) of tissue pathogens. The patient's condition improved after receiving treatment with posaconazole and flucytosine. Patients without underlying diseases rarely develop disseminated Trichosporon asahii infections. In addition to fever, patients with digestive system infections may present with abdominal pain and jaundice. Those with gastrointestinal involvement may develop complications such as anemia and weight loss. Early diagnosis of this disease is difficult, and the mortality rate is high. Voriconazole is the first-choice treatment, and combination antifungal therapy can improve its efficacy.

Attention deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder defined by developmentally inappropriate inattention and/or hyperactivity-impulsivity that impairs daily functioning. Mood disorders are highly prevalent comorbidities in ADHD, exacerbating treatment complexity and exerting adverse effects on core symptom severity and long-term prognosis. This review synthesizes the latest research advances in the epidemiology, pathophysiological mechanisms, assessment-diagnostic strategies, and therapeutic interventions for ADHD comorbid with mood disorders, aiming to provide an evidence-based theoretical foundation for comprehensive clinical diagnosis and integrated management.

Febrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic epileptic encephalopathy that predominantly affects school-aged children.Characterized by a biphasic clinical course, FIRES manifests as rapid progression to refractory status epilepticus following a preceding febrile infection. The prognosis of FIRES is dismal: the acute-phase mortality rate is approximately 10%, and survivors often develop chronic refractory epilepsy and cognitive impairment. The pathogenesis of FIRES remains unclear, but neuroinflammation involving cytokines such as IL-6 may play a key role. Tocilizumab, a humanized monoclonal antibody targeting the IL-6 receptor, exerts anti-inflammatory effects by blocking IL-6 signaling. For FIRES patients unresponsive to conventional anti-seizure medications (ASMs), first-line immunotherapies, or ketogenic diet, tocilizumab is currently recommended as a second-line immunotherapeutic option. This review summarizes the background, mechanisms, clinical applications, safety profile, and challenges associated with tocilizumab in FIRES management, aiming to update clinicians on the latest advances in this field..

Postoperative nausea and vomiting (PONV) is one of the most common complications following pediatric day surgery, with an incidence ranging from 70% to 80%. It significantly impacts patient comfort, recovery progress, and the efficiency of day surgery. With the widespread implementation of the day surgery model in pediatrics, the prevention and management of PONV have become a crucial component of perioperative care. However, factors such as the unique physiological characteristics of children, the diversity of surgical procedures, and the current lack of standardized prevention and management strategies necessitate the systematic integration of existing evidence to guide clinical practice. This review aims to summarize the latest advancements in risk factors, assessment tools, pharmacological and non-pharmacological preventive measures for PONV in pediatric day surgery. It also explores the value of multimodal combined prevention strategies in optimizing PONV management. The goal is to provide scientific and standardized references for clinical practice, thereby improving the surgical experience and recovery quality for pediatric patients.