AIMS:To characterize the clinical, electrophysiological, and genetic spectrum of pediatric CMS and evaluate genotype-informed outcomes using an integrated phenotype-electrophysiology-genomics approach. METHODS:We retrospectively reviewed 36 pediatric CMS patients evaluated at a single center between 2015 and 2025. Clinical features, RNS, targeted NGS/WES variants, ventilator use, treatments, ACMG/AMP classifications, and MG-ADL outcomes were analyzed. RESULTS:Of 36 patients, 28 (77.8%) developed symptoms in the neonatal period or infancy. Biallelic variants involved 17 CMS genes; postsynaptic CMS was most common (55.6%, 20/36). COLQ and CHRNE were the most frequent genes (13.9%, 5/36 each), followed by CHAT (11.1%, 4/36). VUS were detected in 19 patients (52.8%, 19/36), including 8 with biallelic VUS supported by phenotype, neuromuscular transmission findings, treatment response, and follow-up. RNS showed a ≥ 10% decrement in 16/21 tested patients (76.2%). CHAT-CMS was associated with higher ventilator use (3/4 vs. 6/32; p = 0.041) and early mortality (3/4 vs. 1/32; p = 0.002). Median MG-ADL improved from 5 to 3 after genotype-informed therapy. CONCLUSION:Pediatric CMS shows marked genetic heterogeneity and frequent VUS-related uncertainty. Integrating phenotype, electrophysiology, and genomics supports diagnosis and mechanism-guided therapy. CHAT-CMS is high risk for early respiratory failure and mortality.

Objectives: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis that can lead to severe neurological impairments, particularly in pediatric patients. Effective biomarkers for diagnosis and prognosis are crucial for improved treatment outcomes. To evaluate the potential of soluble Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) and serum as diagnostic and prognostic biomarkers in pediatric patients with anti-NMDAR encephalitis. Methods: The study included 21 children diagnosed with anti-NMDAR encephalitis and 27 children with non-inflammatory neurological disorders (OND) as controls. CSF and serum samples were collected from each patient. sTREM2 levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Mann-Whitney U test and ROC curve analysis, were performed to assess the diagnostic and prognostic value of sTREM2. Results: sTREM2 levels in CSF and serum were significantly higher in children with anti-NMDAR encephalitis compared to the OND group (p < 0.001). CSF sTREM2 levels showed a positive correlation with modified Rankin Scale (mRS) scores and a negative correlation with Glasgow Coma Scale (GCS) scores, suggesting an association with disease severity. ROC curve analysis demonstrated that CSF sTREM2 had a high diagnostic accuracy (AUC = 0.887, p < 0.001), while serum sTREM2 showed a slightly lower diagnostic accuracy (AUC = 0.848, p < 0.001). Patients with better prognoses had significantly lower CSF sTREM2 levels than those with poorer outcomes (p = 0.029). Conclusions: Elevated CSF sTREM2 levels were associated with increased neuroinflammation and poorer clinical outcomes in children with anti-NMDAR encephalitis. These findings suggest that CSF sTREM2 may serve as a valuable biomarker for the diagnosis and prognosis of pediatric anti-NMDAR encephalitis.

Background and Objective: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a significant component of demyelinating diseases in pediatric populations. Recently, diagnostic criteria for MOGAD were established. This study aims to evaluate and compare the diagnostic efficacy of the fixed-cell-based assay (Fixed-CBA) and the live cell-based assay (Live-CBA) in patients who meet the 2023 clinical diagnostic criteria for MOGAD. Methods: This retrospective study included patients suspected of having MOGAD who were enrolled between June 2023 and June 2024. Patients were selected based on the “core clinical demyelinating events” outlined in the 2023 proposed criteria of the International MOGAD Panel. Patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 antibody-positive (AQP4-Abs-positive), and non-central nervous system (non-CNS) inflammatory diseases were chosen as controls. Serum samples were simultaneously tested for MOG-Abs using Fixed-CBA and Live-CBA. Results: A total of 86 patients were enrolled in the study: 52 in the suspected MOGAD group and 34 in the control group. Out of these patients studied, 16 presented with optic neuritis (ON), 5 with myelitis, 8 with acute disseminated encephalomyelitis (ADEM), and 7 with cortical encephalitis. Sixteen patients could not be classified by clinical phenotype. The highest MOG-Ab positivity rate was among patients with cortical encephalitis [85.7% (Live-CBA)/71.4% (Fixed-CBA)]. Both assays identified 22 positive samples, with Fixed-CBA and Live-CBA sensitivities at 44.2% and 55.8%, respectively, and a specificity of 97%. Of the patients suspected of having MOGAD, 19 cases were confirmed using the Fixed-CBA, while 28 cases were confirmed using the Live-CBA. This resulted in an upgrade in diagnostic classification for nine cases. This led to a diagnostic reclassification in nine cases. Conclusions: Both the Fixed-CBA and Live-CBA were associated with higher sensitivity for patients selected based on the 2023 MOGAD clinical diagnostic criteria. The Live-CBA exhibited an 11.6% increase in sensitivity, contributing to a 17.3% (9/52) enhancement in clinical diagnostic accuracy.

Objective: The objective of this study was to analyze the clinical phenotypes and genetic variant characteristics of four unrelated Chinese children carrying pathogenic variants in the CTCF gene and to explore the genotype–phenotype heterogeneity of autosomal dominant intellectual disability type 21 (MRD21, OMIM 615,502). Methods: Four pediatric patients admitted to Beijing Children’s Hospital, Capital Medical University, from 2020 to 2024 were enrolled in this retrospective study. All patients underwent medical history collection, physical examination, laboratory tests and high-throughput sequencing. Identified variants were verified in the probands and parents via Sanger sequencing or CNV-seq. Results: Four distinct heterozygous CTCF variants were identified: a missense variant c.1117C>T (p.His373Tyr); an 8.92 Mb microdeletion at 16q21-q22.1 (arr[GRCh37] 16q21q22.1(58,986,875–67,907,636)×1), encompassing the entire CTCF gene; a frameshift deletion c.615_618delGAAA (p.Lys206Profs*15); and an intragenic deletion of exons 8–10. Parental testing confirmed that all identified variants were of de novo origin. The missense variant and the frameshift deletion have been reported previously in ClinVar (VCV000521287.19 and VCV001308122.2), but the two deletions were not found in public databases. Three patients presented with global developmental delay consistent with MRD21, with variable additional features including autistic-like behavior and facial dysmorphism. Notably, two of these patients showed somatic overgrowth with height and weight above the 97th percentile, contrasting with the short stature classically emphasized in MRD21. The fourth patient was a preterm infant with neonatal chylothorax, cardiopulmonary failure, and multiple congenital cardiovascular malformations; developmental assessment at a corrected age of 11 months showed only mild lags. Conclusions: This study expands the spectrum of pathogenic CTCF variants in the Chinese population and underscores the marked phenotypic heterogeneity of CTCF-related disorders, ranging from benign developmental outcomes with complete catch-up to severe neonatal multisystem involvement. In neonates presenting with unexplained chylothorax and multisystem abnormalities, especially when accompanied by features suggestive of a neurodevelopmental syndrome, CTCF should be considered in the differential diagnosis. Given this heterogeneity, a broad genomic approach rather than targeted CTCF screening is recommended in patients with complex presentations.

BACKGROUND:Febrile infection‑related epilepsy syndrome (FIRES) is a severe acute inflammation‑associated encephalopathy in children, characterized by high mortality and poor long‑term outcomes. FIRES with claustrum lesions (FIRES‑C) represents a distinct subtype. However, the relationship between its neuroimaging heterogeneity and electrophysiological phenotype remains unclear, and the association between sleep spindles and acute‑phase severity has not been systematically investigated. This study aimed to characterize the electroclinical features of FIRES‑C to facilitate improvements in diagnosis, treatment, and prognostic evaluation. METHODS:This retrospective study enrolled pediatric patients from our previously reported large cohort. We evaluated dynamic electroencephalographic changes across the acute and chronic phases, examined the correlation between sleep spindles and disease severity, and compared differences between isolated claustrum lesions and those with concurrent thalamic/temporal lobe involvement. All statistical analyses were performed using SPSS 26.0. RESULTS:Twenty-one patients with FIRES-C were included, with a median age of onset of 8.33 years. All presented with focal motor seizures and impaired consciousness. Claustrum lesions appeared >10 days after onset in 90.5% of patients, and 76.2% had additional brain involvement. Among the 19 patients who were followed up, 63.2% achieved favorable long-term outcomes. Acute-phase electroencephalography (EEG) revealed absent occipital rhythm, diffuse delta slowing, disrupted sleep architecture, and migratory focal discharges; EEG abnormalities improved markedly during the chronic phase. Patients without sleep spindles exhibited more severe acute clinical manifestations; however, this finding did not correlate significantly with long-term neurological outcomes. Univariate analyses showed that children with isolated bilateral claustrum lesions had milder acute symptoms and better long-term functional prognosis. In contrast, patients with concomitant thalamic and temporal lobe involvement tended to have impaired consciousness, significantly lower detection rates of sleep spindles on EEG, and poorer long-term functional outcomes. CONCLUSION:FIRES-C exhibits characteristic dynamic EEG evolution. The absence of sleep spindles merely indicates a trend toward more severe acute clinical manifestations and cannot serve as a predictor of long‑term functional prognosis. Univariate intergroup comparisons demonstrated that the extent of imaging lesions was correlated with acute disease severity, EEG findings, and long‑term prognosis.

Importance:Perampanel (PER) is used less extensively in children than in adults. Currently, there is a lack of data from PER clinical studies with large sample sizes in Chinese children and adolescents with epilepsy, especially those with refractory epilepsy. Objective:To evaluate the effectiveness, retention, and safety of PER in the treatment of children and adolescents with epilepsy in China. Methods:This was a multicenter, prospective, observational study. Children and adolescents with epilepsy who received PER as adjunctive therapy were included. The primary effectiveness endpoint was the proportion of patients achieving a ≥50% reduction in seizure frequency after 6 months of treatment compared to baseline. The secondary effectiveness endpoints included retention and seizure-free rates. The safety outcome was the incidence of treatment-emergent adverse events (TEAEs). Results:A total of 240 patients with epilepsy were enrolled in the study. Prior to initiating PER treatment, approximately 87.9% of them took two or more antiseizure medications. After a 6-month treatment regimen with PER, 70.4% of the patients experienced a reduced seizure frequency of at least 50%, and 22.1% achieved complete seizure freedom. The retention rate was 90.2%. TEAEs were reported by 89 patients, leading to the discontinuation of PER in seven cases. No severe TEAEs were observed in this study. Interpretation:Under routine clinical conditions, PER demonstrated good effectiveness and retention in Chinese children with epilepsy, particularly in those with refractory epilepsy.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a neuroinflammatory disorder with a heterogeneous phenotype. MOGAD, presenting with meningoencephalitis, has been described, with limited data on the clinical and radiographic features in children. We aimed to comprehensively investigate the clinical and radiographic characteristics of the MOG antibody-associated meningoencephalitis in children and to identify any magnetic resonance imaging (MRI) markers associated with relapse. This was a single-center, retrospective study. All data for pediatric patients (age of onset < 18 years) diagnosed with MOGAD at our hospital from January 2018 to January 2024 were reviewed. Patients with initial clinicoradiological constellations consistent with meningoencephalitis were included in the analysis and subsequently classified into monophasic and multiphasic groups based on the presence or absence of clinical relapses. A total of 53 children (23

OBJECTIVE:This study aimed to assess the diagnostic value of symmetrical claustrum sign (SCS) in children with febrile infection-related epilepsy syndrome (FIRES), and describe the clinical features, treatment responses, and prognosis of children with FIRES accompanied by symmetrical claustrum lesions (FIRES-C). METHODS:A retrospective cohort study conducted at Beijing Children's Hospital from January 2015 to April 2024 included children with "fever and convulsions" who met the inclusion criteria. The diagnostic efficacy of SCS was calculated by analyzing the sensitivity and specificity. RESULTS:The study enrolled 1105 patients, including 129 with FIRES, 35 of whom were diagnosed with FIRES-C (median onset age: 8.3 years; 18 male). In the cohort of patients with status epilepticus (n = 347), the sensitivity of SCS was 27.1% (95% confidence interval [CI], 19.8%-35.9%), and the specificity was 95.4% (95% CI, 91.8%-97.4%). The median time to develop bilateral claustrum lesions was 15.8 days (interquartile range [IQR] 11-19). The results of the magnetic resonance imaging (MRI) scans revealed that 7 patients (20%) had isolated claustrum lesions, whereas 28 patients (80%) had extra-claustrum lesions. After a median follow-up of 42 months, 14 of the 29 patients (48.3%) who survived exhibited moderate to severe deficits (modified Rankin scale [mRS] ≥3) and 2 patients died. When compared to FIRES patients without claustrum lesions (n = 94), those with FIRES-C (n = 35) demonstrated a tendency toward milder disease severity, characterized by higher Glasgow Coma Scale (GCS) scores and lower incidence of non-midazolam anesthetic use and respiratory support requirements (p < .001). However, no significant differences in prognosis were observed between the two groups (p = .322). SIGNIFICANCE:SCS exhibit high specificity but limited sensitivity in the diagnosis of FIRES in pediatric patients. SCS may serve as a biomarker to assist in the diagnostic process and is typically associated with a less severe clinical progression.

Since meningoencephalitis with prominent meningeal involvement was first described as a rare phenotype of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), sporadic cases have been reported. However, most of the reports were case reports and small sample cohorts. We conducted a retrospective analysis of paediatric patients with MOG antibody-associated meningoencephalitis without cerebral parenchyma involvement on imaging at Beijing Children’s Hospital between 2017 and 2024. Upon reviewing the records of 320 MOG antibody-positive paediatric patients in our centre, we identified 18 (6

BackgroundB3GALNT2 mutations cause α-dystroglycanopathy (α-DGP), a rare condition characterized by muscular dystrophy, brain malformations, and developmental delay. However, its pathogenic mechanisms remain poorly understood. To date, limited cases have been reported, and the pathogenic mechanisms remain incompletely understood.MethodsClinical and genetic data from 3 newly diagnosed Chinese patients and 28 patients previously diagnosed with B3GALNT2-related α-DGP were analyzed. Using patient-derived fibroblasts, α-dystroglycan (α-DG) glycosylation and laminin-binding capacity were assessed by immunoblotting, laminin overlay and immunofluorescence. B3GALNT2 mRNA and protein levels were quantified by real-time PCR and immunoblotting. Enzymatic activity was measured using purified recombinant B3GALNT2 proteins. Differentially expressed genes were identified via an mRNA microarray.ResultsAll three patients carried compound heterozygous variants involving one truncating and one missense mutation. Two novel mutations (c.657_658insTT and c.1384T > C) were identified. Functional studies confirmed that the missense mutations (Y436C and C462R) impaired enzymatic activity to 40-50% of wild-type levels, while splice variants caused frameshifts and likely complete loss of protein. Despite partial residual activity, all patients showed severely reduced α-DG glycosylation and loss of laminin binding, consistent with a functional threshold effect. Transcriptomic analysis revealed upregulation of CHST10 in two patients.ConclusionsThis study expands the mutational spectrum of B3GALNT2-related α-DGP and provides mechanistic insight into the pathogenicity of novel variants. Our findings support a functional threshold model for B3GALNT2 activity in α-DG glycosylation and suggest CHST10 as a potential transcriptional responder to glycosylation defects. These results deepen the understanding of B3GALNT2-related dystroglycanopathies and may inform future diagnostic and therapeutic strategies.

Objective: To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS). Methods: A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children's Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results: There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ²=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ²=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence (OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis (OR=11.64 (1.27-106.72), P=0.030). Conclusions: OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

BACKGROUND AND OBJECTIVES:Paraneoplastic neurologic syndromes (PNSs) are remote neurologic immune-related effects of tumors. The clinical characteristics of pediatric PNSs remain unclear. We retrospectively examined the clinical characteristics of cases of pediatric PNSs and assessed the performance of the 2021 diagnostic criteria in children.METHODS:Patients hospitalized in the Beijing Children's Hospital between June 2015 and June 2023 and fulfilling the description of definite by 2004 diagnostic criteria of PNSs were included. A retrospective analysis of clinical characteristics was conducted, and the 2021 diagnostic criteria were applied to rediagnostic stratification.RESULTS:Among the 42 patients included, the most common neurologic syndrome was opsoclonus-myoclonus syndrome (OMS) (62%), followed by rapidly progressive cerebellar syndrome (26%). Most tumors were neuroblastomas (88%), with few being ovarian teratomas (10%). Approximately 71% (30/42) of patients were classified as definite and 24% (10/42) as probable according to the 2021 criteria. All cases judged as probable exhibited rapidly progressive cerebellar ataxia with neuroblastoma. For OMS, chemotherapy was administered based on the tumor's risk stage, accompanied by regular infusion of IV gamma globulin and oral steroids following tumor diagnosis. Twenty-one patients underwent regular follow-ups over 4.92 (0.58-7.58) years. The initial hospitalization recorded a median score of 12 (7-14) on the Mitchell and Pike OMS rating scale, decreasing to 0 (0-5) at the final follow-up. In cases of rapidly progressive cerebellar syndrome, a similar therapeutic regimen was used. Nine patients underwent regular follow-ups over 4.42 (1.17-7.50) years. The mean modified Rankin scale score at first hospitalization was 4 (3-4), reducing to 1 (0-4) at the final follow-up. Only 17% (5/30) of patients across both groups exhibited poor response to this regimen. Among these 5 patients, 4 belonged to the low-risk group (without chemotherapy).DISCUSSION:OMS followed by rapidly progressive cerebellar ataxia are the most common forms of PNSs in children and are associated with neuroblastoma. An aggressive approach with multiple immunotherapies may improve the prognosis of neuroblastoma-associated PNSs. The 2021 criteria perform well in pediatric PNSs. However, we propose upgrading the classification of antibody-negative rapidly progressive cerebellar ataxia with neuroblastoma to definite diagnosis. This adjustment aims to further improve the diagnostic efficacy of this diagnostic criterion in childhood.

Background: Anti-Purkinje cell cytoplasmic antibody type 2 (PCA-2) is associated with various neurological conditions in adults. However, related studies have not been conducted in children. The present study aimed to characterize the clinical features and outcomes of PCA-2-related autoimmune cerebellar degeneration in pediatric patients. Methods: A total of 357 pediatric patients with acute or subacute cerebellar ataxia were recruited for the study from June 2015 to September 2022. Of these, PCA-2 was identified in four patients. Information on the clinical manifestations, patient response to treatment, and outcomes was collected and analyzed. Results: The patient cohort in the present study included two boys and two girls, with the age of onset from six to 12 years. Axial ataxia was the most remarkable symptom observed in the entire patient cohort (four of four), followed by dysmetria in 75% (three of four), dysarthria in 50% (two of four), and nystagmus in 25% (one of four) of patients. Cognitive impairment was present in one patient. Peripheral neuropathy, which is an extracerebellar symptom, was found in two patients. One patient was diagnosed with a pelvic neuroblastoma before the onset of ataxia. The presence of oligoclonal bands was confirmed in the cerebrospinal fluid, and cerebellar atrophy was observed. Immunotherapy, including glucocorticoids and/or intravenous immunoglobulin, was administered to all four patients immediately following diagnosis, and mycophenolate mofetil was administered to three patients. Three patients responded to immunotherapy. Conclusions: In children, PCA2-associated autoimmune cerebellar degeneration is rare, and they show comparatively fewer symptoms than adults. Timely and appropriate immunotherapy is beneficial. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Objective: To summarize the clinical and genetic characteristics of mental retardation disorder (MRD) with TRIO gene variant in children. Methods: Case series study. The data of 9 children with TRIO gene variants were collected retrospectively from August 2019 to March 2024 in Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University. The data included gender, age, intellectual and motor development, appearance, seizures, neuroimaging and genetic results. The clinical features and genotype-phenotype correlations were summarized. Results: Of the 9 children, 6 boys and 3 girls, 4 MRD63 children presented with moderate to severe developmental delays accompanied by macrocephaly; 5 MRD44 children had mild to moderate developmental delays with microcephaly. A total of 5 children had dysmorphic facial features (flat occiput, thick eyebrows, unibrow, large ears, short fingers, pale skin, yellow hair, and strabismus), 2 children experienced seizures (1 child with myoclonic seizure and 1 with absence seizure), 4 children had feeding difficulties, 1 child had congenital cataracts, 1 child had congenital heart disease, 1 child had recurrent infections, and 1 child had tiger-striped changes in the fundus examination. TRIO gene variants carried by the 9 children were all de novo, involving 8 variant sites, including 7 missense variants and 1 frameshift variant, c.3232C>T/p.R1078W (2 cases), c.3920A>G/p.Y1307C, c.4112A>T/p.H1371L, c.4283G>T/p.R1428L, c.4394A>G/p.N1465S, c.6041T>C/p.I2014T, c.6821G>A/p.R2274H, c.7027delC/p.Q2343Sfs*70. Among them, 2 sites are located in the Spectrin domain, 4 sites are in the GEFD1 domain, 2 sites are in the GEFD2 domain, and 1 site (frameshift variant) is in the PH2-SH3 domain. The individual with frameshift variant exhibit absence seizures, mild developmental delay, and the mildest phenotype. The child with myoclonic seizures was treated with valproic acid and levetiracetam for seizure control, while the child with absence epilepsy was treated with valproic acid and lamotrigine for seizure control. All 9 children underwent regular rehabilitation exercises, making slow progress. Conclusions: TRIO gene related MRD is characterized by varying degrees of developmental delay, and often accompanied by macrocephaly or microcephaly, dysmorphic facial features, and with or without seizures. The main variant types are missense variants, which are mostly concentrated in the Spectran domain and GEFD domain. p. R1078W may be a relative hotspot variant. The phenotype caused by the frameshift variant is relatively milder.

Importance:Aicardi-Goutières syndrome (AGS) is a rare genetic disorder mainly affecting the central nervous system and autoimmunity. However, research on AGS among Chinese patients is limited. Objective:To summarize the neurologic phenotypes and genetic causes in pediatric AGS patients, providing insights for early recognition and diagnosis in the Chinese population. Methods:Clinical features and neuroimaging results of the patients diagnosed with AGS from Beijing Children's Hospital between January 2018 and January 2022 were collected. Whole exome sequencing was used for genetic analysis. Results:A total of 15 patients was included, all presenting with various neurological symptoms, including developmental delay (100%), motor skill impairment (100%), language disability (78.6%), dystonia (93.3%), microcephaly (73.3%), sleep disorders (26.7%), regression (20.0%), vessel disease (6.7%), and epilepsy (6.7%). Neuroimaging revealed intracranial calcification (86.7%), cerebral atrophy (73.3%), and leukodystrophy (73.3%). Seven genes were identified, with TREX1 being the most common (40.0%, 6/15), followed by IFIH1 (20.0%, 3/15). Variant c.294dupA (p.C99Mfs*3) was detected in four unrelated patients, accounting for 66.7% (4/6) patients with the TREX1 variant. A literature review showed that TREX1 gene mutations in 35.6% (21/59) of AGS patients among the Chinese population. Interpretation:Neurological symptoms are the most prevalent and severe presentation of AGS. Diagnosis may be considered when symptoms such as developmental delay, dystonia, microcephaly, brain calcification, and leukodystrophy emerge. TREX1 mutations are predominant in the Chinese population.

Mutations in IBA57 disrupt iron-sulfur clusters maturation, causing a rare mitochondrial disease. Clinical manifestations vary from neonatal lethality to childhood-onset spastic paraparesis, yet the ethnic heterogeneity and natural history remain unclear, necessitating further exploration. This study aimed to delineate the genotype-phenotype correlation of IBA57 mutations by analyzing diverse clinical presentations. We report 11 Chinese patients and include literature-reported cases, totaling 61 patients enrolled for analysis. Clinical, neuroimaging, genetic, and disease progression information were collected. Among these, 46 presented as multiple mitochondrial dysfunctions syndrome 3 (MMDS3), with 58.7% originating from Chinese population. Based on disease course, we propose three clinical subtypes: neonatal, infant and childhood subtypes. Neonatal cases universally displayed hypotonia and respiratory distress at presentation, deceased within three months. Most infancy and childhood cases exhibited developmental regression and impaired motor function. Cavitating leukoencephalopathy was a typical neuroimaging finding in MMDS3 patients. The c.286 T > C mutation was reported in 85.2% of Chinese patients. A significantly lower mortality rate was observed compared to the non-Chinese group (P = 0.002), with a survival rate exceeding 90% at 5 years, indicating a relatively stable disease progression. Fifteen cases from three families manifested the spastic paraplegia 74 phenotype, demonstrating normal development before onset, with common clinical manifestations including spastic paraplegia (14/15), visual impairment (10/13), and peripheral neuropathy (9/13). In conclusion, this study indicates a hotspot mutation in Chinese and analyses the disease progression with different clinical subtypes.

目的 探讨不同年龄段儿童动脉缺血性脑卒中(AIS)的病因.方法 回顾性分析首都医科大学附属北京儿童医院神经内科病房2016年1月至2020年12月收治的AIS患儿资料,根据2019年美国心脏协会和美国卒中协会儿童脑卒中的管理指南将AIS病因分为心源性、易栓症、脑动脉病、其他、病因不详5大类.根据年龄分为婴幼儿(＞28d至＜3岁)、学龄(前)儿童(3～＜10岁)和青少年(10～＜18岁).分析不同病因患儿的临床特点.结果 共纳入129例AIS患儿.脑动脉病是首要病因,共47例(36.43％),最常见的亚型为局灶脑动脉病(FCA,15例)和Moyamoya病(17例).婴幼儿AIS共51例(39.53％),外伤后基底节脑梗死是首要病因(24/51,47.06％),这部分患儿中21例有基底节钙化.学龄(前)儿童AIS共54例(41.86％),青少年AIS共24例(18.60％),两者均以脑动脉病为首要病因.学龄(前)儿童AIS中存在11例病因不详的患儿,均为男性,影像学椎基底动脉供血区有多个梗死灶,不能除外椎动脉夹层,但均未行颈部CTA或MRA检查.青少年AIS中2例患儿经基因检查明确诊断为腺苷酸脱氨酶2缺乏症.结论 不同年龄段儿童AIS病因存在差异,婴幼儿以外伤后基底节脑梗死最为常见,学龄(前)儿童和青少年以脑动脉病最为常见.FCA和Moyamoya病是脑动脉病中最常见的亚型.

BACKGROUND:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. METHODS:This was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. RESULTS:A total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). CONCLUSIONS:The spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.

Objective:To investigate the clinical characteristics, laboratory characteristics and genetic diagnosis of aromatic L-amino acid decarboxylase deficiency (AADCD), and to improve the understanding of this disease.Methods:Four children diagnosed with AADCD from the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to June 2020 were collected, and their clinical manifestations, laboratory and imaging data, and genetic test results were retrospectively analyzed.Results:All the 4 cases were diagnosed in early infancy, with the first symptom of feeding difficulties. They developed paroxysmal dyspraxia accompanied by eye movement crisis, movement regression, hypotonia, growth retardation, sleep disorders and autonomic nervous symptoms such as ptosis, excessive sweating and nasal congestion at the age of 2-4 months, respectively. The 4 children were siblings from 2 families with healthy parents. The dihydroxyphenylalanine decarboxylase ( DDC) gene mutations in cases 1 and 2 were derived from the maternal missense mutation c.1040G>A(P.RG347gln), and from the paternal deletion of exons 11 and 12, respectively. The DDC gene mutation in case 3 was derived from the maternal mutation c.419G>A(p.G140E) and the paternal mutation c.1375C>T(p.H459Y), respectively. Case 4 did not undergo genetic testing. Blood amino acid and acylcarnitine profiles and urine organic acid analyses were performed in 3 cases, and no specific abnormalities were found. In case 3, the results of 3-O-methyldopa (3-OMD) screening by blood dry filter paper increased significantly. Cerebrospinal fluid neurotransmitter detection results showed that the concentrations of 3-methoxy-4-hydroxyphenyldiol, vanillic acid and 5-hydroxyindoleacetic acid were significantly decreased, while the levels of 5-hydroxytryptophan and 3-OMD were increased in case 3. Blood aromatic L-amino acid decarboxylase (AADC) activity decreased significantly in case 3. Cranial magnetic resonance imaging (MRI) and electroencephalogram (EEG) examinations were performed in cases 1, 3, and 4, among which the cranial MRI in case 1 was normal, while the cranial MRI in cases 3 and 4 suggested that myelination was slightly backward. The EEG was normal in all the 3 cases. Cases 1 and 2 died of pneumonia and respiratory failure at the age of 1 year and 10 months. Case 3 was given clonazepam, benxel hydrochloride tablets and vitamin B6 tablets orally after diagnosis at the age of 4 months, and then treated with selegiline hydrochloride tablets and pramexol hydrochloride tablets. At the follow-up of 1 year and 6 months, the frequency of eye movement crisis and movement disorder was reduced, sleep was improved and autonomic nervous symptoms were alleviated, but there was no improvement in developmental delay. Case 4 was diagnosed with cerebral palsy and epilepsy, but failed various antiepileptic drugs and rehabilitation training, and died at the age of 10 due to heart failure and kidney failure. Conclusions:The clinical manifestations of AADCD are complicated and the misdiagnosis rate is high. Infants with early-onset hypotonia, developmental retardation, eye movement crisis, and movement disorders should be screened with dry filter paper as soon as possible for 3-OMD level, and suspicious cases should be diagnosed by cerebrospinal fluid neurotransmitter detection, plasma AADC activity determination, and gene examination. Early diagnosis of AADCD in children and gene mutation carriers can guide treatment and provide genetic counseling to reduce the incidence of the offspring.

Neutral lipid-storage disease with myopathy (NLSDM) is an autosomal recessive neuromuscular disorder caused by mutations in PNPLA2, and the average age at onset is 30 years. To date, only eight patients with childhood-onset NLSDM have been reported in detail. We investigated 3 unreported patients with NLSDM detected in childhood and reviewed 8 childhood-onset and 82 adult-onset patients with NLSDM documented in the literature. In the childhood-onset cohort, NLSDM presented initially as asymptomatic or paucisymptomatic hyperCKemia in 6/11 patients, and follow-up data showed onset of muscle weakness in 6/11 childhood-onset patients. In the adult-onset cohort, 95.1% (78/82) of patients showed muscle weakness. Cardiac involvement developed in 6/11 childhood-onset patients. Hepatomegaly was observed in 3/11 childhood-onset patients. Serum creatine kinase levels were elevated greater than five-fold of the upper limit of normal (ULN) in most childhood-onset patients and were elevated to less than ten-fold of the ULN in most adult-onset patients. Peripheral blood smears and muscle biopsies showed cytoplasmic lipid droplets in leukocytes and myocytes. NLSDM can present in children with asymptomatic or paucisymptomatic hyperCKemia before the onset of muscle weakness. The presence of lipid droplets in leucocytes (Jordans' anomaly) aids in diagnosing and confirming the pathogenicity of PNPLA2 variants of uncertain significance. There were no clear genotype-phenotype correlations in patients with NLSDM.