Objective To investigate the cranial magnetic resonance imaging （MRI） features of patients with hepatolenticular degeneration （also known as Wilson disease，WD） and epilepsy， and to identify the neuroimaging risk factors for seizures in WD patients. Methods A total of 69 WD patients with epilepsy who were hospitalized in Affiliated Hospital of Neurology Institute， Anhui University of Chinese Medicine， from January 2018 to November 2025 were enrolled as study group， while 80 WD patients without seizures， matched for sex and age， during the same period of time were randomly selected as control group. Cranial MRI findings were compared between the two groups. Results There were 69 WD patients （43 male patients and 26 female patients） in the study group， with a mean age of （29.46±8.58） years at the time of attending the hospital， and all these patients had abnormal electroencephalogram （EEG） findings. There were no significant differences between the two groups in age of onset，disease duration， WD subtype， and serum copper. Cranial MRI showed that the putamen was the most common site of brain injury （47 patients， 68.1%）， followed by the frontal lobe （40 patients，58.0%） and the parietal lobe （31 patients，44.9%）， and there was a significantly higher probability of epilepsy in patients with abnormal lesions in the frontal， temporal， or parietal lobes （P<0.05）. Conclusion While the putamen is the most common site of brain injury in WD patients with epilepsy， frontal or temporal lobe injuries are neuroimaging risk factors for seizures in such patients.
Epilepsy, Frontal Lobe ; Putamen

OBJECTIVE: To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS). METHODS: A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital of Zhengzhou University (Ethics No. 2024-KY-1103-001). RESULTS: The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c.1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The hemizygous c.1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.
Humans ; Male ; Infant ; Microcephaly/genetics* ; Spasms, Infantile/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing ; Intellectual Disability/genetics* ; Genetic Diseases, X-Linked/genetics* ; Mutation ; Seizures/genetics* ; Ataxia ; Epilepsy ; Ocular Motility Disorders

OBJECTIVE: To investigate the clinical phenotype and genotype features of children with Epileptic encephalopathy caused by PCDH19 mutations. METHODS: Four children with epilepsy caused by PCDH19 gene mutations who were treated at Shanghai Children's Medical Center from August 2015 to May 2024 were selected as study subjects. A retrospective study method was used to collect the clinical data of the patients. Peripheral venous blood samples (2 mL each) were collected from the patients and their parents. Genomic DNA was extracted, and whole exome sequencing (WES) was performed, followed by family verification of candidate variants by Sanger sequencing. Pathogenicity of the candidate variants was classified according to the "Genetic Variation Classification Standards and Guidelines" established by the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Shanghai Children's Medical Center (Approval No. SCMCIRB-K2020060-1). RESULTS: The patients comprised of 3 females and 1 male, all presenting symptoms before the age of 3. Patients 1-3 exhibited generalized tonic-clonic seizures, while patient 4 manifested focal seizures accompanied by impaired consciousness. In addition to epilepsy, patient 2 showed language delay and patient 3 had frequent panic attacks. WES results identified four pathogenic PCDH19 variants these patients, including 2 previously unreported frameshifting mutations,1 hotspot missense mutation, and 1 mosaic missense mutation with a 32.4% mutation rate. The pathogenic mutation in patient 2 was inherited from her father, while the remaining 3 patients had de novo pathogenic mutations. CONCLUSION Children with PCDH19 gene mutations may exhibit early-onset refractory epilepsy, cognitive impairment, and developmental delay. Females are predominantly affected by the PCDH19 mutations, although males with mosaic mutations can also be affected. The genetic and clinical heterogeneity observed among patients 1-4 indicated the diverse nature of epilepsy related to the PCDH19 gene mutations. PCDH19 gene mutations may be the genetic cause of epilepsy in these affected children, which also enriched the mutational spectrum of the PCDH19 gene.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Cadherins/genetics* ; Epilepsy/genetics* ; Exome Sequencing ; Mutation ; Phenotype ; Protocadherins ; Retrospective Studies

OBJECTIVE: To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. METHODS: A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using "SETD1B" and "epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. RESULTS: The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely c.5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no significant difference in incidence between males and females. CONCLUSION SETD1B gene variants may cause neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.
Humans ; Female ; Child ; Epilepsy/genetics* ; Language Development Disorders/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Exome Sequencing ; Male

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a child with Cortical dysplasia, complex, with other brain malformations 4 (CDCBM4) and epilepsy due to a TUBG1 gene variant. METHODS: A child diagnosed with CDCBM4 and epilepsy at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in May 2024 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral venous blood samples were collected from the child and her parents for genomic DNA extraction. Trio-based whole-exome sequencing (WES) was performed, and candidate variants were validated by Sanger sequencing. According to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG), candidate variants were classified for pathogenicity. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Guangdong Medical University (Ethics No.: PJ2021-097). RESULTS: The child, a 4-month-old female infant, had no special facial features, normal limb muscle strength, and increased muscle tone of infantile onset, with generalized tonic-clonic seizures as the main manifestation. During seizures, she exhibited head retroflexion, tightly closed eyes, and tonic convulsions of the limbs, occurring approximately 2-3 times per day. Electroencephalogram suggested bilateral anterior predominant medium-to-high amplitude 7-8 Hz mixed rhythm discharges. Head MRI revealed ventricular system dilatation and pachygyria. Trio-WES results indicated that the child has harbored a TUBG1 gene variant of c.776C>T (p.Ser259Leu). Sanger sequencing verification showed that neither of her parents had carried the same variant, confirming it as de novo in origin. According to the ACMG guidelines, the variant was rated as pathogenic (PS2+PS3+PM2_Supporting+PP3). Combining the child's clinical phenotype, the child was diagnosed as CDCBM4 with epilepsy. CONCLUSION Children with CDCBM4 and epilepsy due to TUBG1 gene variants may show pachygyria or agyria and commonly present with intellectual and motor developmental delays and seizure disorders of variable severity. The heterozygous TUBG1 c.776C>T (p.Ser259Leu) variant is likely the genetic etiology underlying this disorder. The results of this study has expanded the mutational spectrum of the TUBG1 gene associated with CDCBM4 and epilepsy.
Humans ; Female ; Epilepsy/genetics* ; Malformations of Cortical Development/genetics* ; Infant ; Phenotype ; Exome Sequencing ; Microtubule-Associated Proteins/genetics*

OBJECTIVE: To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy. METHODS: A total of 91 children with epilepsy admitted to the Women's and Children's Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women's and Children's Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048). RESULTS: Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. CONCLUSION Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.
Humans ; Female ; Male ; Epilepsy/genetics* ; Child, Preschool ; Child ; Phenotype ; Genotype ; DNA Copy Number Variations/genetics* ; Infant ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics* ; Adolescent ; Exome Sequencing

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with Fliedner-Zweier syndrome (FZS). METHODS: A pregnant woman who was diagnosed with FZS at the Affiliated Women and Children's Hospital of Ningbo University in November 2023 for "intellectual disability, epilepsy, delayed language development and facial abnormalities" was selected as the study subject. Peripheral blood samples were collected from the woman and her husband, whilst amniotic fluid sample was obtained from the fetus. Following extraction of genomic DNA, whole-exome sequencing (WES) and chromosomal karyotyping analysis were performed. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: The proband, a 23-year-old woman, was at 19⁺² weeks of gestation and had a history of epilepsy, mild intellectual disability, delayed language development, and subtle facial dysmorphism. Chromosomal analysis showed the she has a normal karyotype. WES revealed that the woman and her fetus both harbored a heterozygous c.1489C>T (p.Gln497Ter) nonsense variant of the SCAF4 gene, which was verified by Sanger sequencing as de novo. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_supporting+PS2_supporting). According to pre-set search strategy, five articles were retrieved. Together with the patient in this study, a total of 69 FZS patients were involved (including 7 from China). The main clinical features have included intellectual disability, epilepsy, behavioral abnormalities, and facial dysmorphism. CONCLUSION The heterozygous c.1489C>T (p.Gln497Ter) variant of the SCAF4 gene probably underlyay the FZS in this patient. Above finding has expanded the mutational spectrum of the SCAF4 gene.
Humans ; Female ; Intellectual Disability/genetics* ; Pregnancy ; Young Adult ; Exome Sequencing ; Epilepsy/genetics* ; Abnormalities, Multiple/genetics* ; Mutation ; Karyotyping

OBJECTIVES: To investigate the efficacy and safety of perampanel (PER) add-on therapy in children with epilepsy of genetic etiology. METHODS: A retrospective analysis was conducted on the clinical data of 53 children who attended the Department of Neurology, Wuhan Children's Hospital, from November 2020 to April 2023. All children received PER add-on therapy and were diagnosed with epilepsy of genetic etiology based on whole-exome sequencing. The primary outcome measure was the proportion of children with a reduction in seizure frequency of ≥50% at month 12 of PER treatment (i.e., response rate), and the secondary outcome measures were response rates at months 3 and 6 of treatment. The influencing factors for the efficacy of PER add-on therapy in the treatment of epilepsy of genetic etiology were analyzed, and adverse events were recorded. RESULTS: The median follow-up duration was 13.10 months. After 12 months of follow-up, 42 children were included in the analysis, comprising 25 boys (60%) and 17 girls (40%). The median initial dose of PER was 1.5 (1.0, 2.0) mg/d, and the median maintenance dose was 4.0 (3.0, 8.0) mg/d. The response rates to PER at months 3, 6, and 12 of treatment were 61% (30/49), 54% (25/46), and 48% (20/42), respectively. No significant difference in the efficacy of PER was observed between children with mutations in genes encoding different protein functions (P>0.05). The most common adverse event reported was fatigue, observed in 3 children (6%). CONCLUSIONS PER add-on therapy demonstrates good efficacy and safety in children with epilepsy of genetic etiology. No influencing factors for the efficacy of PER have been identified to date.
Humans ; Male ; Female ; Nitriles ; Child ; Pyridones/administration & dosage* ; Child, Preschool ; Retrospective Studies ; Anticonvulsants/administration & dosage* ; Epilepsy/etiology* ; Adolescent ; Infant ; Drug Therapy, Combination

OBJECTIVES: To summarize the clinical and genetic characteristics of epilepsy with intellectual disability caused by SETD1B gene variants in children. METHODS: A retrospective analysis was conducted on the clinical data of three children with SETD1B gene variants diagnosed and treated at the Department of Pediatric Neurology of Xiangya Hospital of Central South University. Relevant literature was reviewed to summarize the clinical characteristics of this condition. RESULTS: All three children presented with symptoms during infancy or early childhood, including mild intellectual disability and myoclonic seizures, with two cases exhibiting eyelid myoclonia. After treatment with three or more antiepileptic drugs, two cases achieved seizure control or partial control, while one case remained refractory. Each of the three children was found to have a heterozygous variant in the SETD1B gene (one deletion, one frameshift, and one missense variant). To date, 54 cases with SETD1B gene variants have been reported, involving a total of 56 variants, predominantly missense variants (64%, 36/56). The main clinical manifestations included varying degrees of developmental delay (96%, 52/54) and seizures (81%, 44/54). Among the 44 patients with seizures, myoclonic (20%, 9/44) and absence seizures (34%, 15/44) were common, with eyelid myoclonia reported in six cases. Approximately one-fifth of these patients had poorly controlled seizures. CONCLUSIONS The primary phenotypes associated with SETD1B gene variants are intellectual disability and seizures, and seizures exhibit distinct characteristics. Eyelid myoclonia is not uncommon.
Humans ; Intellectual Disability/complications* ; Epilepsy/complications* ; Male ; Female ; Histone-Lysine N-Methyltransferase/genetics* ; Child, Preschool ; Child ; Retrospective Studies

The patient was a girl, aged 10 years, who was admitted due to fever for 5 days and pancytopenia in peripheral blood for 2 days. Bone marrow examination showed the presence of phagocytic activity, and peripheral blood tests showed pancytopenia, an increase in ferritin, a reduction in fibrinogen, increases in triglyceride and sCD25, and a reduction in natural killer cell activity, which led to the diagnosis of hemophagocytic lymphohistiocytosis (HLH). On the day of admission, the child developed convulsions and rapidly progressed to refractory status epilepticus, which was consistent with the manifestations of febrile infection-related epilepsy syndrome. HLH was controlled after active immunotherapy, with the sequela of refractory epilepsy, and her cognitive function was essentially within normal limits. This article reports the condition of febrile infection-related epilepsy syndrome caused by HLH for the first time in China, in order to improve the awareness of this disease among clinicians.
Humans ; Lymphohistiocytosis, Hemophagocytic/complications* ; Female ; Child ; Epilepsy/etiology* ; Fever/etiology* ; Epileptic Syndromes/etiology*