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Objective:To investigate the clinical phenotype and genetic characteristics of infantile epileptic spasm syndrome caused by BRWD3 gene mutation. Methods:Clinical data of a child with BRWD3 related infantile epileptic spasm syndrome who was admitted to Department of Pediatric Neurology of Linyi People′s Hospital on August 2, 2019 were collected and followed up, whole exome sequencing technology and Sanger sequencing were applied to verify the child and his parents, and the pathogenicity of mutation site was analyzed. The studies till June 2023 were searched with keywords of " BRWD3" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical phenotype and genetic characteristics of patients with BRWD3 related epilepsy were summarized. Results:The patient was a 4 years and 4 months old boy, with a clinical phenotype including severe global development delay, focal seizures (the onset age was 4 months), epileptic spasm (the onset age was 6 months), autism, megacephaly, high forehead as well as hypsarrhythmia. The whole exome sequencing results showed a de novo and frameshift variation c.4318_4319del(p.Q1441Efs*20)(NM_153252) in the BRWD3 gene, and the variation was interpreted as pathogenic (PVS1+PS2+PM2) according to the American College of Medical Genetics and Genomics variant classification criteria and guidelines. A total of 7 English literature articles were retrieved reporting 16 cases of BRWD3 gene related epilepsy in children (including 1 case of infantile epileptic spasm syndrome), and there has been no report in China yet. Totally there were 17 cases of BRWD3 gene related epilepsy including this case. All the cases showed X chromosome dominant inheritance, of whom 15 cases showed minor variations, including 7 missense variations, 3 frameshift variations, 3 splicing variations, 2 nonsense variations, and the remaining 2 cases showed large segment deletions. A total of 15 different variants were found. The phenotypes of the 17 patients mainly included epileptic seizures (17/17), intellectual disability (10/17), motor development disorder (7/17), speech impairment (9/17), megacephaly (8/17), facial malformation (8/17), autism (4/17) and hypotonia (4/17). The common seizure types were found to be focal seizures, occasionally epileptic spasm seizures and tonic seizures. Conclusions:BRWD3 gene variation related epilepsy is an X chromosome dominant genetic disease with a wide clinical phenotype spectrum. BRWD3 gene mutation c.4318_4319del(p.Q1441Efs *20) could cause infantile epileptic spasm syndrome, manifested as severe global developmental delay, epileptic spasm, focal seizures, autism, craniofacial malformation and hypsarrhythmia. This research enriches BRWD3 gene mutation spectrum.
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Infantile epileptic spasm syndrome (IESS) is a new concept proposed recently. IESS is a unique and age-specific refractory epilepsy syndrome. The recent advances in molecular biology, neuroimmunology and the in-depth study of anti-epileptic mechanism in antiepileptic drugs have led to the achievements in the definition and treatment of infantile epileptic spasm. At present, the use of traditional antiepileptic drugs is decreasing, while the use of new antiepileptic drugs is increasing. In this paper, based on the relevant literature in recent years, the authors discuss the pathogenesis, epidemiology, etiology, diagnosis, treatment, therapeutic drugs, clinical progress, efficacy, and safety of infantile epileptic spasm, hoping to introduce the latest status in research and achievements of IESS.
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OBJECTIVES@#To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS).@*METHODS@#A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity.@*RESULTS@#Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05).@*CONCLUSIONS@#Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.
Subject(s)
Child , Humans , Infant , Nonlinear Dynamics , Spasms, Infantile , Retrospective Studies , Brain , ElectroencephalographyABSTRACT
We reported a case of microcephaly-capillary malformation(MIC-CAP)caused by STAMBP gene variant,in order to improve the clinical diagnosis and treatment.The patient is a 3-month-old male with recurrent convulsions and the main clinical manifestations are multiple forms of seizures,microcephaly,multiple small capillary malformations in the skin,and generalized hypotonia.The genetic test showed that a heterozygous variant in the STAMBP gene was present in the child.Both parents were heterozygous carriers.He was administrated various anti-seizure medications and ketogenic diet,but still had frequent seizures.He then underwent corpus callosotomy,and was followed up until he was 4 years and 10 months old.The post operational outcome was grade IV on Engel's classification.Based on the clinical data of 22 patients in literature,in addition to severe psychomotor retardation,microcephaly,and cutaneous capillary malformations,early-onset drug-refractory epilepsy is also a major feature of MIC-CAP syndrome,which is clinically rare and has a poor prognosis;Callosotomy may help to reduce seizures in the short term.However,the long-term outcome is poor.STAMBP gene is the main responsible gene for this syndrome.
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Objective:To analyze the clinical characteristics of late-onset epileptic spasm (LOS), thus providing basis for its early identification and treatment.Methods:Clinical data[electroencephalogram(EEG), imaging, treatment and prognosis]of LOS patient hospitalized in the Department of Pediatrics, the Second Affiliated Hospital of Xi′an Jiaotong University from January 2017 to June 2019 were retrospectively analyzed.Results:The age of onset of spasm in 35 children with LOS ranged from 18 months to 11 years old, with a median of 42 months.There were 21 cases of symptomatic LOS (60.0%) and 14 cases of cryptogenic LOS (40.0%). Epileptic spastic seizures, generalized seizures, partial seizures and myoclonic seizures as the first onset were reported in 13 cases (37.1%), 11 cases (31.4%), 10 cases (28.6%), and 1 case (2.9%), respectively.There were 15 cases (43.9%) of flexion type, 11 cases (30.4%) of extension type and 9 cases (25.7%) of mixed type.Spastic seizures can be presented as genera-lized or focal seizures.Among the 35 cases of LOS, 12 cases (34.3%) had normal EEG background, 18 cases (51.4%) had slow EEG background, and 5 cases (14.3%) had high EEG irregularity.Three cases were in accor-dance with Lennox-Gastaut syndrome and the other 32 cases were not in accordance with the defined epileptic syndrome.Eighteen cases were treated with antiepileptic drugs, and sodium channel blockers were added in 9 cases; 17 cases were treated with glucocorticoid.Eight cases did not have seizures at the last follow-up.There were 17 children with seizure reduction ≥ 50%, 3 cases with seizure reduction < 50%, and 7 cases with no reduction of seizure.Conclusions:LOS is mostly symptomatic and often associated with other types of seizures.Most of cases do not have high irregularity in the EEG, and the focal discharges are mainly in the temporal region or frontotemporal region, with refractory epilepsy mainly.The onset age, etiology and EEG characteristics of LOS differ from those of West syndrome, which should be detected and treated as soon as possible to improve the prognosis in pediatric patients.