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Objective:To investigate the expression of stanniocalcin-2 (STC-2) and cellular-mesenchymal epithelial transition factor (C-met) in tumor tissues of cervical cancer patients and their clinical significance.Methods:A total of 110 cervical cancer patients were selected in Foshan First People′s Hospital from January 2014 to December 2018. Patients′ cancer tissue samples and normal tissue samples were collected during modified radical resection to determine and compare the expression levels of STC-2 mRNA and C-met mRNA in the two tissues, and to analyze the correlation between the expression levels of STC-2, C-met and the clinicopathological characteristics of the patients as well as the multivariate analysis of tumor metastasis and recurrence in the patients. The correlation between the expression of STC-2 and C-met and the time of postoperative tumor metastasis and recurrence in cervical cancer patients were analyzed after 24 months of follow-up.Results:The expression levels of C-met mRNA and STC-2 mRNA in cancer tissues were higher than those in adjacent normal tissues: 4.51 ± 1.21 vs. 3.97 ± 1.14, 2.57 ± 0.21 vs. 2.12 ± 0.24, there were statistical differences ( t = 3.41, 14.80, P<0.05). The expression of STC-2 and C-met in cancer tissues had no significant difference with age, pathological type, federation international of gynecology and obstetrics (FIGO) stage and tumor size ( P>0.05), but had significant difference with tumor recurrence or metastasis ( P<0.05). The results of Logistic multivariate analysis showed that vascular emboli, lymph node metastasis, TNM stage, depth of tumor invasion, C-met expression and STC-2 expression were independent risk factors affecting the prognosis of cervical cancer patients ( P<0.05). The expression of STC-2 and C-met were negatively correlated with the time of tumor metastasis in patients with cervical cancer ( r = - 0.663, P<0.001; r = - 0.747, P<0.001). Conclusions:The expression levels of STC-2 and C-met in cancer tissues of cervical cancer patients are higher than those in adjacent normal tissues, and the expression levels of STC-2 and C-met are negatively correlated with the time of metastasis. The expression of C-met, the expression of STC-2, vascular emboli, lymph node metastasis, TNM stage, and the depth of tumor invasion are all independent risk factors affecting the prognosis of cervical cancer patients.
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Objective:To analyze the clinical phenotype and genotype characteristics of infantile spasm (IS) associated with UBA5 gene mutation. Methods:Four cases of IS caused by UBA5 gene variation diagnosed at the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were retrospectively analyzed.The clinical manifestations, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), treatment, and follow-up results were summarized. Results:In this study, 4 cases (3 males and 1 female) were clinically diagnosed with IS and carried complex heterozygous variation of UBA5 gene.Genetic analysis confirmed that a total of 6 different mutation sites were found, five of which were unreported.All the 4 cases presented with epileptic spasms at the age of 1 d to 8 months after birth, and 2 cases had focal seizures during the course of disease.The EEG of 4 cases showed hypsarrhythmia and cluster or isolated epileptic spasms were detected.Of the 3 patients who had brain MRI results, 2 cases showed nonspecific abnormalities and 1 case was normal.All the 4 patients had developmental delayed before seizure onset, and regressed to varying degrees and made slow progress after onset.One case had microcephaly, and 3 cases had hypertonia.At the last follow-up, the age of the 4 patients ranged from 7 months to 6 years and 4 months.All 4 patients were treated with multiple antiepileptic drugs, but none of them were under control. Conclusions:Children with IS associated with UBA5 gene variation have an early onset age, often accompanied by developmental delayed, microcephaly, dystonia, and refractory seizures.
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Objective:To summarize the clinical features of developmental epileptic encephalopathy children with DNM1 gene variants. Methods:The genotypes and clinical features of 15 children with DNM1 variants related epilepsy in the Department of Pediatrics, Peking University First Hospital from June 2017 to October 2021 were retrospectively analyzed. Results:A total of 8 male and 7 female epilepsy patients with DNM1 gene variants with the age of seizure onset ranging from 15 days to 22 months were recruited, median age was 8 months.All cases belonged to de novo heterozygous variants of the DNM1 gene, including 13 cases of missense variants, 1 case of frame shift variant and 1 case of nonsense variant, 8 cases of ectopic sites have not been reported.Multiple seizure types were observed, including epileptic spasms in 15 patients, focal seizure in 9 patients, atypical absence seizure in 2 patients and tonic seizure in 2 patients.There were various types of seizures in 7 children.Nine cases occurred as infantile spasm for the first time.All 15 patients showed varied degrees of development delay, among them, 11 cases had developmental retardation before epilepsy.Three patients had slow rhythm of electroencephalogram background activity, the electroencephalography showed hypsarrhythmia in 13 patients; clinical seizures were detected in 8 cases, among them, epileptic spasms were captured in 7 patients, tonic seizure was captured in 1 patient.Widened frontotemporal subarachnoid space, cerebral atrophy, and corpus callosum dysplasia were examined in 6, 2 and 3 patients by cranial magnetic resonance imaging, respectively.All 15 cases were diagnosed as developmental epileptic encephalopathy, of which 13 cases were consistent with infantile spasms.The age of the last follow-up ranged from 1 year old to 7 years old.After multi-antiepileptic drug treatment, 2 patients were remission, 1 patient(small size of identical twins) died of severe pneumonia at the age of 2 years, and 12 patients still had intermittent seizures, of which 1 patient was transformed from infantile spasms to Lennox-Gastaut syndrome. Conclusions:The onset age of developmental epileptic encephalopathy caused by the DNM1 gene variant usually begins in the infantile period, the peak onset age was 8 months.The main types of seizures include epileptic spasms and focal seizures, developmental retardation can occur before seizures.The clinical manifestations are mostly infantile spasms syndrome, and some children can be transformed into Lennox-Gastaut syndrome.
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Objective:To summarize the therapeutic effect of deep brain stimulation (DBS) for dystonia.Methods:Detailed clinical information and peripheral blood of children with dystonia at Peking University First Hospital from April 2017 to July 2020 were collected.The motor scores of Burke-Fahn-Marsden Dystonia Rating Scale were recorded of the dystonia before and after the treatment of DBS.Whole-exome sequencing was performed on children with dystonia.Then the effect of DBS was evaluated.Results:A total of 32 cases of patients with dystonia treated with DBS were enrolled, including 16 males and 16 females.Twelve cases were treated with globus pallidus internus DBS, and 20 cases were treated with subthalamic nucleus DBS.Twenty cases (62.5%) with pathogenic gene mutations were detected.Pathogenic variants in PANK2 (9 cases), KMT2B(3 cases), GNAO1 (2 cases), GCDH (2 cases), PINK1(1 case), NDUFAF6(1 case), DYT27(1 case) and ADCY5(1 case) were found.The follow-up period was 1 month to 3 years and 8 months.Only 1 case had local infection due to improper home care.The postoperative improvement was 5.66%-95.92%. Conclusions:All patients have a certain degree of relief after DBS without obvious adverse reactions.DBS is an effective treatment for pediatric dystonia.
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Objective:To study the clinical and genetics features of two families with dentatorubral-pallido-luysian atrophy (DRPLA), and to summarize the correlation between genotypes and phenotypes.Methods:The peripheral blood, clinical data and auxiliary examination results of probands and related members in 2 families with hereditary epilepsy and ataxia were collected from July 2018 to March 2019 in Peking University First Hospital.By whole exome sequencing and detecting the cytosine-adenine-guanine (CAG) repeats with capillary electrophoresis and fragment analysis, the genetic testing was conducted on the probands and their family members.The clinical and genetic characteristics of all affected members in the 2 families were also analyzed.Results:Two families were diagnosed with DRPLA.All 11 patients presented with psychomotor retardation, and 7 of them had seizures (including myoclonus, focal seizures and generalized tonic-clonic seizures, etc.). There were significant differences in clinical manifestations among different patients in the same family, and the filial generation had seizures at an earlier age with a more severe phenotype than the parental generation.The youngest onset age was 2 years old, and the largest was 45 years old.Five cases had seizures in childhood.Of the 11 patients, 5 cases were deceased, and the cause of death included seizure attacks, sudden unexpected death in epilepsy (SUDEP) and disease progression.The number of CAG repeat times in the fifth exon of the ATN1 gene were found abnormal in 6 surviving patients.The grandfather of the proband in pedigree 2 had normal clinical manifestations, but he also showed abnormal CAG repeats in the fifth exon of the ATN1 gene, which might be an intermediate allele. Conclusions:DRPLA is mainly featured by epilepsy, ataxia, psychomotor retardation and anticipation in clinical.This disease is rare in children with seizures as the first symptom, and has poor prognosis.An early diagnosis can facilitate genetic counseling.
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Objective:To analyze the clinical phenotype and genetic characteristics of children with germline PIGA gene mutations. Methods:The clinical presentations, blood biochemistry, electroencephalogram (EEG), brain magnetic resonance imaging (MRI) and genetic test results of 10 children diagnosed at the Department of Pediatrics of Peking University First Hospital between January 2014 and June 2020 were analyzed.Results:All these 10 children were male, with seizures and severe developmental delay.Five out of eight cases showed hypotonia.Four out of nine cases had facial deformity or multiple organ abnormalities.The onset age of seizures ranged from one month and 28 days to 10 months, with an average age of 4.8 months.There were various types of seizures, and all patients showed focal seizures.The seizures of 6 patients in these 10 cases could be induced by fever disease.Diffuse slow waves mixed focal or multifocal discharges of interictal EEG in 9 cases with PIGA-deficient.Brain MRI showed enlarged subarachnoid space in 44.4% (4/9 cases) of patients.Slight elevated serum alkaline phosphatase could be seen in 2 cases.Genetic analysis confirmed that a total of 8 different mutation sites were found, 7 of which were unreported.In this group, 4 cases were diagnosed with multiple congenital anomalies -hypotonia -seizures syndrome 2 (MCAHS2), 5 cases were diagnosed with developmental delay and epilepsy without deformity, and one case was not classified, respectively. Conclusions:Focal seizure was common in these patients with PIGA mutations, and often induced by fever disease.Interictal EEG was characterized by diffuse slow waves mixed focal or multifocal discharges.Enlarged subarachnoid space was the most common brain MRI abnormality in these patients.The phenotype of patients only partially conformed to typical MCAHS2 manifestations, and most of them had no deformity.
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Objective:To investigate the normal range of exhaled nitric oxide (FeNO) in 6-18-year-old children in China, so as to provide a data base for the establishment of FeNO standards for Chinese children.Methods:A multi-center study was conducted on 5 949 children aged 6-18 (3 101 males and 2 848 females) in 16 pro-vinces of 7 administrative districts in China.According to the technical standard recommended by American Thoracic Society/European Respiratory Association, FeNO was measured, and the relationship of FeNO with the sex, age, height, weight, body mass index and region was discussed.Results:The geometric mean FeNO value of Chinese children aged 6-18 was 14.1 ppb, and its 95% confidence interval (skewness distribution) was 1.0-38.2 ppb.The geometric mean FeNO values of children aged 6-11 and 12-18 were 13.1 ppb and 15.7 ppb, respectively, and their 95% confidence intervals (skewness distribution) were 1.0-38.1 ppb and 2.0-38.2 ppb.For children at and under 11 years old, FeNO decreased with age, with a mean decline of 1 ppb per year.The multiple linear regression results suggested that there was a significant correlation between FeNO and age for children aged 6-11, and FeNO of children aged 12-18 was significantly correlated with the gender, height, and region(all P<0.01). Conclusions:FeNO values of Chinese children and adolescents in this study are higher than those obtained by the previous study conducted from 2010 to 2012.For children aged 12-18, 16 ppb is recommended as the clinical cut-off point.For children at or under 11 years old, the influence of age on FeNO should be considered, and the cut-off point of FeNO decreases by 1 ppb as the age is reduced by one year.
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Objective:To summarize the genotypes and phenotypes of children with ALG13 gene related congenital disorders of glycosylation type Ⅰ. Methods:Four epilepsy patients with ALG13 variants visiting the Department of Pediatrics, Peking University First Hospital from January 2016 to July 2019 were included.Their clinical data and gene results were analyzed. Results:There were 1 boy and 3 girls.Three patients had p. N107S variant, and 1 case had p. W112X variant.Two patients inherited the variants from their asymptomatic mother and 2 patients had de novo variants.The seizure began at 3 months to 2 years old.Focal seizure was observed in 1 patient, and epileptic spasms in 2 patients.Focal seizure, tonic seizure and epileptic spasms were observed in 1 patient simultaneously.Three patients were diagnosed with infantile spasms.All patients with ALG13 variants had developmental delay, including autistic-like features in 3 cases, hypotonia in 2 cases, and visual disorders in 1 case.The electroencephalography showed hypsarrhythmia in 3 children, and focal spikes and waves in 1 child, and spasms in 2 children.The brain magnetic resonance imaging showed cerebral atrophy in 1 patient, while the other 3 cases were normal.The last follow-up age was 2 years and 2 months to 4 years and 4 months.Four patients still had frequent seizures after treatment with antiepileptic drugs. Conclusions:ALG13 variants were mainly de novo, and p. N107S is a hot variant.ALG13 gene variations mainly occur to infants, characterized by developmental delay and spasms.Infantile spasm is the most common phenotype.Some patients have autistic-like features, hypotonia, visual disorders and cerebral atrophy.
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Objective:To follow up and clarify the prognosis of 670 pediatric patients with Dravet syndrome (DS).Methods:The clinical data of DS pediatric patients treated in the Department of Pediatrics, Peking University First Hospital from February 2005 to August 2016 were recorded, and genetic testing was carried out.DS pediatric patients were followed up via subsequent visits at the outpatient and telephone interview.Results:Among 670 cases with DS, 556 cases (556/670 cases, 83.0%) carried SCN1A mutations.In the follow-up, 608 cases were contacted (608/670 cases, 90.7%) and 62 cases (62/670 cases, 9.3%) were lost.The last follow-up median age was 8 years 5 months.Eighty-two cases (82/608 cases, 13.5%) were seizure-free for more than 1 year, with a median age of 9 years and 2 months.Thirty-eight cases relapsed (38/82 cases, 46.3%), mainly induced by fever (34 cases) or mi-ssing antiepileptic drugs (2 cases). Analysis of the relative factors of patients that were seizure-free for more than 1 year showed that children with missense SCN1A mutations, inherited mutations and an older age had a relatively good outcome for seizure control.Twenty-five cases (25/608 cases, 4.1%) were deceased, with a median age of 4 years.The mortality factors included multiple organ dysfunction syndromes after prolonged status epilepticus (12 cases), possible sudden unexpected death in epilepsy (7 cases), asphyxiation after vomiting with or without a seizure (2 cases), and an accidental injury (1 case). The fatal causes in the remaining 3 cases were unknown. Conclusions:DS is an intractable epileptic syndrome, but few patients may have a seizure remission (seizure free for more than 1 year). Patients with mi-ssense SCN1A mutations, inherited mutations and an older age have a relatively good outcome for seizure control.The mortality rate is high in DS patients.The causes of mortality include multiple organ dysfunction syndromes after prolonged status epilepticus, possible sudden unexpected death in epilepsy, and so on.
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Objective:To summarize the clinical phenotype and gene mutation characteristics of male patients with epilepsy caused by mosaic PCDH19 mutation. Methods:The clinical data of 3 male patients with epilepsy caused by mosaic PCDH19 mutation were analyzed.Microdroplet digital polymerase chain reaction (mDDPCR) was used for the detection of mosaicism in the three probands and their family members.Relevant literatures were reviewed. Results:The seizure onset age were 5 months, 9 months and 6 months of life respectively.Focal seizures occurred in 2 cases and multiple seizure types occurred in 1 case.Three patients presented with clusters of seizures.Fever sensitivity was observed in 2 cases out of the 3 cases.Two patients had intellectual disability and 1 patient had autistic manifestation.The clinical phenotype in 2 patient fulfilled the diagnosis of Dravet syndrome. PCDH19 mosaic mutations c. 317T>A(p.M106K), c.158dupT(p.D54Gfs*35) and c. 1639G>C(p.A547P) were detected respectively, and were identified as de novo after parental validation.Mutant allele fractions (MAF) in the blood samples were identified as 81.18%, 37.08%, 77.64%, respectively.The MAF of multiple tissues in 1 patient varied from 78.67% to 98.46%.Review of literature revealed that a total of 11 cases with mosaic PCDH19 mutation were reported.Among them, seizure onset occurred between 5 and 31 months of age.Focal seizures occurred in 9 cases, 3 cases of the 9 cases had only focal seizures.Generalized tonic clonic seizures occurred in 4 cases.Two or more seizures were observed in 6 cases.Clustering of seizures was found in all patient and sensitivity to fever was observed in 9 patients.Seven patients had mild to severe intellectual disability and 5 patients had autistic features. Conclusions:The clinical phenotypes of male patients with epilepsy caused by PCDH19 mosaic mutation are characterized by clustering of seizures, sensitivity to fever, focal seizures in most cases, varied degree of intellectual disability and autistic features in partial.
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Objective@#To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants.@*Methods@#The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children′s Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. The clinical features and gene test results were analyzed retrospectively.@*Results@#Data of 9 patients (4 boys and 5 girls) diagnosed as myoclonus dystonia syndrome caused by SGCE variants were collected. The onset age ranged from 1 year to 3 years and 2 months. The first symptom was myoclonus in 4 cases, while dystonia in the remaining 5 cases. In the course of the disease, 9 cases had myoclonus and 8 had dystonia. Myoclonic jerks were characterized by involuntary jerks in both upper limbs in 8 patients. Six patients had involuntary jerks of lower limbs, resulting in gait instability or even falling. The myoclonus was exacerbated during the fine motor activities, emotional stress or fatigue. Dystonia was characterized by abnormal gait, including 5 cases with right leg dystonia, and 3 cases with the left leg dystonia. Three probands had a positive family history. Intellectual development was normal in all cases. There was no obvious abnormality in video-electroencephalogram (EEG) during both ictal and interictal periods. Electromyography (EMG) and brain magnetic resonance imaging (MRI) of 9 patients were normal. Nine patients carried SGCE gene variants, including 3 frame shift variants, 2 nonsense variants, 2 missense variants, 1 fragment deletion variant and 1 splice site variant. Seven variants were inherited paternally, and 2 variants were de novo. Madopar was used in 8 patients, and nitrazepam in 4 patients, leading to the decrease in the myoclonus jerks and improvement of gait in 6 and 2 patients, respectively.@*Conclusions@#SGCE gene variants can cause myoclonus dystonia syndrome. The onset of the disease may occur at infancy or preschool age, with either myoclonic jerks or dystonia as the initial symptom. Non-epileptic myoclonus is the prominent symptom, with upper limb mainly involved. Most of the patients have the accompanying symptoms of dystonia, and some of them may have spontaneous symptom relief. SGCE gene is imprinted maternally, and the inherited variants of SGCE are paternal in origin.
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Objective@#To summarize the clinical phenotypes of epilepsy in patients with GABRA1 gene variants.@*Methods@#A total of 11 epileptic patients (4 boys and 7 girls) who were treated in the Department of Pediatrics, Peking University First Hospital from March 2016 to July 2019 and detected with GABRA1 gene heterozygous pathogenic variants by targeted next-generation sequencing were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively.@*Results@#A total of 11 epileptic patients carried GABRA1 gene pathogenic variants, of whom 10 were de novo variants and the other one was inherited from the patient′s mother. Two patients had the same variants. Six variants were novel. Ages at seizure onset ranged from 3 to 14 months, and the median age was 8 months. The seizure was first observed within 1 year in 10 patients and beyond 1 year of age in 1 patient. Multiple seizure types were observed, including focal seizures in 10 patients, generalized tonic clonic seizures (GTCS) in 3 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. There were 5 patients with multiple seizure types. Sensitivity to fever was observed in 9 patients, among whom 6 patients had a history of status epilepticus. Two patients had photoparoxysmal response. Five patients had abnormal EEG background, and 6 patients had abnormal discharges in EEG during interictal phase. Brain magnetic resonance imaging (MRI) was normal in all patients. Developmental delay in various degrees was present in 9 patients. Among the 11 patients, Dravet syndrome was diagnosed in 5 patients, West syndrome in 2 patients, undiagnosed early-onset epileptic encephalopathy in 1 patient, and focal epilepsy in the other 3 patients. The ages at the last follow-up ranged from 8 months to 12 years. During follow-up, 8 patients were seizure-free for 6 months to 8 years, and 1 patient had discontinuation of medication.@*Conclusions@#In epilepsy associated with GABRA1 gene variants, de novo pathogenic variants are more common than inherited. Most epilepsy caused by GABRA1 gene variants occurs in infancy. Most patients have multiple seizures and focal seizures are common. Most patients have a comparatively favorable prognosis, but they may still have varied degrees of developmental delay.
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Objective@#To investigate the genotype and phenotype of children with KCNA2 gene related developmental and epileptic encephalopathy (DEE).@*Methods@#Clinical data including the manifestations and electroencephalogram of 8 children with KCNA2 variants treated in the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were collected and analyzed retrospectively.@*Results@#Among the 8 epileptic patients with KCNA2 variants, 5 were males and 3 were females. The age of onset was from 1 day to 11 months. The age at last follow-up ranged from 4 months to 86 months. Two variants including c.1214C>T (loss-of-function) and c.1120A>G (gain-and loss-of-function) were identified. The variant of c.1214C>T was found in six patients (case 1-6). For these patients, the age of onset was from 5 to 11 months and they were characterized by multiple seizure types. All had focal seizures and had normal development before seizure onset with developmental regression after seizure onset. The first electroencephalogram showed epileptic discharges in Rolandic region in two, epileptic discharges in Rolandic region combined with generalized discharge in one, generalized discharge with posterior predominance in two (combined with or transferred to Rolandic region during the course) and epileptic discharges in posterior region combined with generalized discharge in one. And in 5 of them the Rolandic discharges developed into epileptic electrical status (ESES) during sleep. All the six patients were still treated with a combination of multiple antiepileptic drugs. Two of them had seizure controlled at 80 months and 68 months, respectively. The variant of c.1120A>G were identified in two of eight patients (case 7 and 8) and they had seizure onset on the 1st day after birth. Their epileptic seizures were frequent and difficult to control. They had remarkably developmental delay and microcephaly since birth. One case (case 8) had a wide forehead. They had frequent seizures up to the last follow-up. In case 7, the early electroencephalogram showed epileptic discharges in temporal region, and interictal electroencephalogram at 3 months of age showed multifocal discharge with posterior and temporal region predominance. In case 8, the early electroencephalogram was normal and electroencephalogram showed burst suppression at 2 months of age, and it developed epileptiform discharge in posterior region at 1 year of age.@*Conclusions@#KCNA2 gene variants can lead to DEE with multiple seizures types. Among them, loss-of-function c.1214C>T is the most common, and these patients have seizure onset at infancy with Rolandic discharges tended to develop into to ESES pattern. The variant of c.1120A>G is a gain-of- and loss-of-function variant, patients with c.1120A>G have seizure onset in neonatal period, the phenotype overlaps with the former but is more severe.
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Objective@#To analyze the clinical phenotypes of epilepsies in children with GABRB2 variants.@*Methods@#Data of 8 epileptic patients with heterozygous GABRB2 variants were retrospectively collected at the Department of Pediatrics, Peking University First Hospital from April 2016 to December 2018. The clinical, electroencephalographic, neuroimaging characteristics, therapeutic and follow-up were analyzed.@*Results@#Eight patients (4 boys, 4 girls) with heterozygous GABRB2 gene pathogenic variants were enrolled. Eight patients had different GABRB2 variants, among whom 2 patients inherited the variants from either parent, and the other 6 patients had de novo variants. Seven variants were novel. Ages at seizure onset ranged from 1 day to 22 months after birth, and the median age was 6 months. The seizure was first observed within one month of age in 2 patients, 1-6 months in 2 patients, 7-12 months in 2 patients, and beyond 1 year of age in 2 patients. Multiple seizure types were observed, including focal seizures in 6 patients, generalized tonic clonic seizures (GTCS) in 4 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. Developmental delay was present in 6 patients. In 8 patients, Dravet syndrome was diagnosed in 3 patients, febrile seizures plus and West syndrome in 2 patients, respectively, Ohtahara syndrome in 1 patient. Six patients had epilepsy with fever sensitivity, and status epilepticus developed in all these patients. The ages at the last follow-up ranged from 8 months to 11 years, and the follow-up data showed that 5 patients were seizure-free, and 2 patients still had seizures, and 1 patient died of recurrent status epilepticus complicated with fungal infection.@*Conclusions@#Epilepsies associated with GABRB2 variants were characterized by an onset in infancy, and the clinical features were heterogenous in seizure types and severities. Most patients had multiple seizures with fever sensitivity, and status epilepticus was common. Their seizures were easily induced by fever or infection. Additionally, the majority of the patients had varying degrees of developmental delay.
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Objective@#To explore clinical features and the effect of treatment of neuromyelitis optica spectrum disorders (NMOSD) in childhood.@*Methods@#Children who were hospitalized in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2018 and meeting diagnostic criteria of NMOSD proposed by the International Panel for NMOSD Diagnosis in 2015 were summarized and followed up. The basic information, symptoms of each attack, locations and patterns of new lesions, features of cerebrospinal fluid, serologic markers, treatments and outcomes in these patients were analyzed. Thirty-three children were included in the study, with 13 males and 20 females. The median age of onset was 6.83 (4.25, 8.75) years. Compared aquaporin-4 immunoglobulin G (AQP4-IgG) associated NMOSD with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated NMOSD. Mann-Whitney U test was used for continuous variables and Fisher test for categorical variables in comparison between AQP4-IgG and MOG-IgG associated NMOSD. Wilcoxon test was used for annualized relapse rate (ARR) before and after adding disease-modifying drugs.@*Results@#Optic neuritis (39% (13/33) in initial attacks and 49% (62/127) in total attacks) and myelitis (36% (12/33) in initial attacks and 26% (33/127) in total attacks) were the top two symptoms in both the initial attacks and all 127 attacks during follow-up. There was 42% (37/89) of brain magnetic resonance imaging (MRI) scans in acute phase showing new lesions in supratentorial white matter, with 43% (16/37) showing acute disseminated encepha lomyelitis (ADEM)-like or leukodystrophy-like patterns. AQP4-IgG was detected in 30% (10/33) patients, and MOG-IgG was detected in 55% (11/20) patients, with no combined positive case. In 20 patients treated with rituximab, two were treated after the initial attack. In the other 18 patients, the median annualized relapse rate decreased from 1.86 (1.52, 2.60) before treatment to 0.28 (0, 1.13) during treatment (Z=-3.376, P=0.001). Compared with AQP4-IgG associated NMOSD (10 cases), fever of unknown origin (8/40 vs. 0/33, P=0.007) was more common, area postrema syndrome (0/40 vs. 4/33, P=0.038) was fewer, cell count of cerebrospinal fluid (49.0 (17.5, 115.0) ×106/L vs. 5.5 (3.0, 15.8)×106/L, Z=-3.526, P=0.000) was higher in MOG-IgG associated NMOSD (11 cases).@*Conclusions@#In childhood-onset NMOSD, optic neuritis and myelitis were top two symptoms. Childhood-onset NMOSD has high proportion of positive MOG-IgG. Lesions in supratentorial white matter are common. Rituximab could significantly decrease ARR of NMOSD in childhood. However, more studies should be conducted to explore the optimal treatment strategy in different antibody associated NMOSD.
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Objective To investigate the clinical and electroencephalogram (EEG) characteristics and treatment of ring chromosome 14 syndrome,and to improve its early recognition and accurate diagnosis.Methods The clinical and EEG characteristics of 4 patients with ring chromosome 14 syndrome confirmed by genetic diagnosis were analyzed in the neurology outpatient department and ward of pediatrics in Peking University First Hospital from August 2012 to August 2018.The treatment and prognosis of the 4 patients were followed up.Results Of the 4 patients,there were 2 males and 2 females.All the patients had developmental delay,abnormal facial features such as wide eye spacing,low nasal bridge and microcephaly.Seizures occurred in all the patients with varying onset ages from 8 months to 1 year.Seizure types included focal seizure,tonic seizure and generalized tonic-clonic seizure.EEG monitoring ages varied from 9 months to 4 years and 4 months.The characteristic EEG pattern manifested as slow activity of background,unilateral or bilateral anterior,posterior or diffuse slow activity,with or without interposed multifocal epileptiform discharges.Cranial magnetic resonance imaging (MRI) showed non-specific abnormality in 1 patient and normal in 3 patients.The ages at the last follow-up ranged from 1 year and 8 months to 7 years and 1 month with intervals from 9 months to 6 years and 5 months.Valproic acid combined with other antiepileptic drugs was used to treat seizures.Seizure reduction instead of control was observed in all the 4 cases.At the last follow-up,the development of movement and language were all delayed in the 4 patients.One case could walk independently,three could walk unsteadily alone;two could speak 2-3 simple words,one could call only " baba,mama",and one had no language development.Conclusions The ring chromosome 14 syndrome is a rare disease caused by chromosome abnormality.Its main clinical manifestations included facial abnormalities,microcephaly,epilepsy,developmental delay especially for language and cognitive disability.The types of seizures included both focal and generalized.EEG showed non-specific features with slow background activity,with the migratory slow waves mixing multi-focal discharges as the main common pattern.The epilepsy of this disease was often drug resistant.Valproic acid combined with other antiepileptic drugs could reduce seizures.Seizures without control could further affect development outcome.
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Objective@#To summarize the clinical phenotype and genotype features of 3 children with progre-ssive myoclonic epilepsy (PME) caused by KCNC1 gene mutations, and to review the related literatures.@*Methods@#The phenotype and genotype of 3 children with KCNC1 mutations in the Department of Pediatrics, Peking University First Hospital from October 2016 to January 2019 were analyzed.The 25 patients with KCNC1 mutations which had been reported internationally were also collected and analyzed.@*Results@#Three children in this study were identified with KCNC1 de novo mutations, in which 2 children were identified with c. 959G>A (p.Arg320His) mutation, and 1 child with c. 1262C>T (p.Ala421Val) mutation.The clinical features of 3 children were consistent with PME, and the seizure onset ages were 3 months, 10 years and 11 years, respectively.Three children all had myoclonic seizures, among whom 1 child had generalized tonic-clonic seizure and 2 children had focal seizures.Three children all had intellectual and/or motor development delay.The electroencephalograph showed generalized spike and waves or polyspike and waves in 3 children, and focal discharge in 2 children.The brain imaging of 3 children was normal.The last follow-up ages were 3 years old, 13 years old and 12 years old, respectively.Until March 2019, there were 25 cases with KCNC1 gene mutations reported internationally.Including 3 patients in this study, there were 28 patients in total, of which 25 patients were diagnosed with PME.In these 25 patients, 24 patients were identified with p. Arg320His variant in the transmembrane area, 1 patient was identified with p. Ala421Val variant in the transmembrane area.The remaining 3 patients were only found with psychomotor developmental delay without seizures, and they were identified with p. Arg339X variant in the intracellular area.In the 28 patients, 16 cases received cranial imaging data, in which 12 patients had ce-rebellar atrophy and 4 cases were normal.Of the 28 patients, 18 cases were mentally retarded, 27 cases were development retardation or retrogression among whom 9 cases could not walk independently.Ten patients were over 30 years old when reported, and only 1 patient died of pneumonia and respiratory failure at 63 years old.@*Conclusions@#KCNC1 gene mutation mainly leads to PME phenotype, and a few patients can only show mental retardation.p.Arg320His is the most common variant of KCNC1 gene.The variants in different structural regions result in different clinical phenotypes, and variants in the transmembrane region can lead to severer clinical phenotypes.The 3 patients with KCNC1 gene mutations in this study are firstly reported cases in China.
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Objective@#To investigate the clinical and electroencephalogram (EEG) characteristics and treatment of ring chromosome 14 syndrome, and to improve its early recognition and accurate diagnosis.@*Methods@#The cli-nical and EEG characteristics of 4 patients with ring chromosome 14 syndrome confirmed by genetic diagnosis were analyzed in the neurology outpatient department and ward of pediatrics in Peking University First Hospital from August 2012 to August 2018.The treatment and prognosis of the 4 patients were followed up.@*Results@#Of the 4 patients, there were 2 males and 2 females.All the patients had developmental delay, abnormal facial features such as wide eye spacing, low nasal bridge and microcephaly.Seizures occurred in all the patients with varying onset ages from 8 months to 1 year.Seizure types included focal seizure, tonic seizure and generalized tonic-clonic seizure.EEG monitoring ages varied from 9 months to 4 years and 4 months.The characteristic EEG pattern manifested as slow activity of background, unilateral or bilateral anterior, posterior or diffuse slow activity, with or without interposed multifocal epileptiform discharges.Cranial magnetic resonance imaging (MRI) showed non-specific abnormality in 1 patient and normal in 3 patients.The ages at the last follow-up ranged from 1 year and 8 months to 7 years and 1 month with intervals from 9 months to 6 years and 5 months.Valproic acid combined with other antiepileptic drugs was used to treat seizures.Seizure reduction instead of control was observed in all the 4 cases.At the last follow-up, the development of movement and language were all delayed in the 4 patients.One case could walk independently, three could walk unsteadily alone; two could speak 2-3 simple words, one could call only " baba, mama" , and one had no language development.@*Conclusions@#The ring chromosome 14 syndrome is a rare disease caused by chromosome abnormality.Its main clinical manifestations included facial abnormalities, microcephaly, epilepsy, developmental delay especially for language and cognitive disability.The types of seizures included both focal and generalized.EEG showed non-specific features with slow background activity, with the migratory slow waves mixing multi-focal discharges as the main common pattern.The epilepsy of this disease was often drug resistant.Valproic acid combined with other antiepileptic drugs could reduce seizures.Seizures without control could further affect development outcome.
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Objective@#To analyze the clinical characteristics of patients with PCDH19-female limited epilepsy (PCDH19-FE).@*Methods@#The clinical data of 60 female epilepsy patients with PCDH19 gene heterozygous variations at the Department of Pediatrics, Peking University First Hospital from October 2007 to December 2018 were collected and analyzed retrospectively, their clinical manifestations, accessory examination and follow-up treatment were summarized.@*Results@#Data of a total of 60 cases of PCDH19-FE were collected. The seizure onset occurred between 4 and 42 months of age (median: 11 months of age). Focal seizures occurred in 47 patients (78%), generalized tonic-clonic seizures (GTCS) occurred in 30 patients (50%), and other rare types of seizures included atypical absence, myoclonic, clonic, tonic, and atonic seizures. Two or more seizures types existed in 24 patients (40%), and seven patients (12%) had attacks of status epilepticus. Sensitivity to fever was observed in 47 out of them (78%) and clustering of seizures as found in all patients. During the interictal phase, focal discharges were monitored in 22 cases (22/45, 49%), multifocal discharges in 12 cases (12/45, 27%), widely discharging in 2 cases (4%), and both focal and widely discharging in 9 cases (20%). Clinical seizures were detected in 30 patients during the electroencephalogram (EEG) recording, including focal seizures in 22 cases, GTCS seizures in 8 cases, tonic seizure in three cases, myoclonic seizure followed by GTCS in one case, and two types of seizures in four cases. Before seizure onset, 57 patients had normal development and three patients had delayed language development. After seizure onset, varied degrees of intelligence disability were present in 38 cases (63%), language delay in 36 cases (60%), and gait instability in 10 cases (17%). Autistic features occurred in 17 cases (28%); and other behavioral problems like learning difficulties, personality, or emotional disorders existed in 33 cases (55%). Age at last follow-up ranged from one year and 3 months to 22 years and 3 months of age, 17 patients (28%) were seizure-free for more than 2 years (5 to 22 years at the last follow-up). The efficiency of antiepileptic drugs were 65% (33/51) in sodium valproate, 63% (27/43) in levetiracetam and 59% (20/34) in topiramate.@*Conclusions@#The clinical features of PCDH19-FE are characterized by clustering of seizures, focal seizures in most cases, sensitivity to fever mostly, focal discharges principally in EEG, varied degrees of intellectual disability or movement disorder, combined with autism spectrum disorders in partial and high efficiency in sodium valproate or levetiracetam treatment.