Objective:To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing. Methods:The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University, from February 2019 to November 2022 were retrospectively analyzed. Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant. The characteristics of the GRIN2A gene variants were analyzed. Results:Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants, the male-to-female ratio was 4∶1, and the age range of onset was 1.5-4.4 years. The clinical phenotype included seizures in all cases, language and intellectual developmental deficits in 4 cases, and attention deficit hyperactivity disorder in 3 cases. The seizures were manifested as focal seizures or secondary generalized seizures, and were effectively controlled with antiepileptic drugs. Among the 5 children, gene variant of case 1 was originated from a paternal heterozygous variant, and cases 2-5 had de novo variants, which were c.2107C>T (p.Gln703 *) nonsense variant, c.2284G>A (p.Gly762Arg) missense variant, c.2197del (p.Ala733Glnfs *3) shifted coding variant, c.2511G>A (p.Trp837 *) nonsense variant, and c.1651+1G>C shear site variant, respectively. None of the 5 loci were reported in the literature. Conclusions:Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset, and may have different phenotypes at different genetic variant loci, with focal seizures or secondary generalized seizures, which can be effectively controlled with anti-seizure medication. The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.

Objective:To summarize the clinical phenotype and genetic characteristics of children with neurodegeneration caused by UBTF gene mutations in childhood. Methods:The clinical and genetic data of 3 children with neurodegeneration in childhood diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University from February 2020 to January 2023 were retrospectively analyzed. All the 3 probands were found having UBTF gene mutations through the whole exome gene sequencing, and the first generation Sanger sequencing method was used to verify the UBTF gene in their family members. The variation characteristics of the UBTF gene were analyzed, and the treatment and follow-up results of the 3 children were summarized. Results:Among the 3 children with childhood onset neurodegeneration, 2 were male and 1 female, aged 9 months, 4 years and 6 months after birth, respectively. The clinical phenotypes mainly included motor retardation, speech and mental retardation, and dystonia. Among them, case 1 and case 2 had seizures, case 1 had dysphagia, feeding problems, no weight gain and ataxia. Brain MRI plain scan showed that case 1 and case 2 had different degrees of cerebral atrophy, case 1 had hypoplasia of corpus callosum, ventricle expansion and softening focus, and case 3 showed non-specific widening of the subarachnoid space. There were no abnormalities in the chromosome copy number variation and mitochondrial ring gene testing in the 3 children; the whole exon gene testing suggested the de novo missense variant in the UBTF gene [NM_014233.4: c.1414(exon14) G>A (p.Gly472Ser), c.1392(exon14)G>T(p.Lys464Asn)] and the maternal nonsense variant [NM_014233.4:c.520C>T(p.Arg174 *)], which were unreported site variants. In terms of treatment, the 3 children received comprehensive rehabilitation function training, and achieved a certain degree of language and intelligence improvement. Seizure control was effectively managed in case 1 with a single antiepileptic drug. Epileptic seizures were effectively treated and controlled in case 2 using more than 4 types of antiepileptic drugs. Conclusions:Neurodegenerative changes caused by UBTF gene mutations in childhood are relatively rare, and some cases may be accompanied with brain atrophy. De novo missense variation and maternal nonsense variation of the UBTF gene are the genetic etiology of the 3 probands.

Objective:To summarize the clinical phenotype and CUX2 gene variation characteristics of developmental epileptic encephalopathy type 67 confirmed by whole exome sequencing. Methods:Clinical data of 1 case diagnosed as CUX2 gene mutations related developmental epileptic encephalopathy type 67 in the Children′s Hospital Affiliated to Zhengzhou University in January 2021 were collected, the patient′s clinical characteristics, genetic testing, head imaging, electroencephalogram results and treatment were summarized, and the patient was regularly followed-up every 3 months. At the same time, the domestic and foreign literatures on epileptic encephalopathy caused by CUX2 gene mutation were reviewed. Results:The proband was a 6 years and 4 months old girl. The main clinical manifestations included focal origin progression to bilateral tonic-clonic seizures, retardation of intellectual, language, and motor development, autistic behavior, hyperactivity disorder, and involuntary hand clapping. The video electroencephalogram showed extensive spiny slow wave and multi-spiny slow wave emission in waking and sleeping stages, and spiny slow wave and spiky slow wave emission in bilateral anterior head in sleeping stage. Brain magnetic resonance imaging (MRI) plain scan and T 2-fluid attenuated inversion recovery (T 2-FLAIR) thin layer scan showed that the signal of the left hippocampus was higher than that of the right, and the left hippocampus was slightly swollen. One month later, the brain MRI and T 2-FLAIR were reexamined. The left hippocampal signal was still slightly higher and decreased, and the hippocampal volume was slightly reduced. Whole exome sequencing showed the CUX2 gene with c.1768G>A(p.Glu590Lys) heterozygous missense variant, which was a reported de novo pathogenic variant and both of her parents were wild-type. A total of 10 cases of new heterozygous missense variants in CUX2 gene [c.1768G>A (p.Gelu590Lys)] were reported in 4 literatures. No relevant cases have been reported in China. Conclusions:Developmental epileptic encephalopathy type 67 is relatively rare. The main clinical features are seizures, global developmental delay, movement disorders, athetosis, autism and hyperactivity disorder. The heterozygous missense variant c.1768G>A (Glu590Lys) of CUX2 gene maybe the genetic cause of this case.

Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.

We reported a 65-year-old female who was admitted to our institute with "recurrent subxiphoid pain accompanied by dyspnea for more than 10 days". Electrocardiogram examination suggested acute extensive anterior ST segment elevation myocardial infarction. Preoperative transthoracic echocardiography suggested ventricular septal rupture. The patient was planned for the repair of ventricular septal rupture with cardiopulmonary bypass. The formation of left ventricular aneurysm was diagnosed by intraoperative transesophageal echocardiography (TEE). The surgeon decided to abdopt the modified incision of left ventricular approach guided by TEE, which greatly improved the prognosis of the patient. The surgery duration was 197 min, aortic cross-clamping time was 56 min, cardiopulmonary bypass time was 69 min, and the patient was safely admitted to ICU after the surgery. Extubation was performed on the first day postoperatively, and the intra-aortic balloon pump support was retreated on the second day postoperatively. Postoperative echocardiography showed that no obvious residual shunt was observed after ventricular septal repairment and ventricular aneurysm resection. The patient was discharged on the 12th day after the surgery. Additionally, the mental condition was good and daily activities were not limited within 6 months postoperatively.

Objective:To analyze the clinical and imaging characteristics of acute necrotic encephalopathy (ANE) in a child with human herpesvirus-6 (HHV-6) infection.Methods:Retrospective analysis was performed on the clinical data and imaging features of a case of HHV-6 related ANE from Children′s Hospital Affiliated to Zhengzhou University in March 2019.Results:The one year and seven month-old child had acute encephalopathy, recurrent convulsions, consciousness disorders, elevated serum transaminase. The number of cerebrospinal fluid (CSF) cells was normal and the protein increased. High throughput gene testing of CSF showed HHV-6. Cranial magnetic resonance imaging showed multiple symmetry damage in the bilateral thalamus, brainstem, and cerebellum. The symptoms improved after the treatment of glucocorticoids, intravenous immunoglobulin, and plasmapheresis.Conclusions:ANE is a rare severe encephalopathy, the characteristic imaging change of which is symmetry multifocal cerebral damage, especially in the bilateral thalamus. ANE should be considered for patients with frequent convulsions and disturbance of consciousness after virus infection.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) emerges in China, which spreads rapidly and becomes a public health emergency of international concern. Chinese government has promptly taken quarantine measures to block the transmission of the COVID-19, which may cause deleterious consequences on everyone's behaviors and psychological health. Few studies have examined the associations between behavioral and mental health in different endemic areas. This study aimed to describe screen time (ST), physical activity (PA), and depressive symptoms, as well as their associations among Chinese college students according to different epidemic areas. METHODS: The study design is cross-sectional using online survey, from 4 to 12 February 2020, 14,789 college students accomplished this online study, participants who did not complete the questionnaire were excluded, and finally this study included 11,787 college students from China. RESULTS: The average age of participants was 20.51 ± 1.88 years. 57.1% of the college students were male. In total, 25.9% of college students reported depression symptoms. ST > 4 h/day was positively correlated with depressive symptoms (β = 0.48, 95%CI 0.37-0.59). COVID-19ST > 1 h/day was positively correlated with depressive symptoms (β = 0.54, 95%CI 0.43-0.65), compared with COVID-19ST ≤ 0.5 h/day. Compared with PA ≥ 3 day/week, PA < 3 day/week was positively associated with depression symptoms (β = 0.01, 95%CI 0.008-0.012). Compared with low ST and high PA, there was an interaction association between high ST and low PA on depression (β = 0.31, 95%CI 0.26-0.36). Compared with low COVID-19ST and high PA, there was an interaction association between high COVID-19ST and low PA on depression (β = 0.37, 95%CI 0.32-0.43). There were also current residence areas differences. CONCLUSIONS Our findings identified that high ST or low PA was positively associated with depressive symptoms independently, and there was also an interactive effect between ST and PA on depressive symptoms.
Adult ; COVID-19/psychology* ; China/epidemiology* ; Cross-Sectional Studies ; Depression/etiology* ; Exercise ; Female ; Humans ; Male ; Mental Health/statistics & numerical data* ; Screen Time ; Students/psychology* ; Time Factors ; Universities ; Young Adult

Objective:To summarize the clinical features of a family of neurofibromatosis type I (NF1) and its NF1 gene mutation characteristics. Methods:The clinical data of a family of NF1 admitted to our hospital in May 2020 were collected. The proband was sequenced with NF1/ NF2 panel using second-generation sequencing. Sanger sequencing verification analysis was performed on the family members. The clinical characteristics of the proband and other family members were summarized and their gene mutations were analyzed. Results:The proband (V 2), a 1-year and 2-month old girl, had multiple Café au lait spots on the skin at birth, normal mental and motor development, and focal epileptic seizures in infancy. The father (IV 3), grandmother (III 2), and other 2 family members (II 2, I 2) in the family all had Café au lait spots or neurofibromatous changes without seizures. The mother's phenotype was normal. The proband had a heterozygous mutation in the NF1 gene, and the mutation site C.83-84delAG (P.N29Hfs*8) was a frameshift heterozygous mutation. After verification analysis by Sanger sequencing, the pathogenic genes of the father and grandmother were consistent with the proband, which was in line with the characteristics of heterozygous mutation in NF1 gene, dominant inheritance. Conclusion:NF1 is caused by NF1 gene mutation; the early clinical manifestations mostly include café-au-lait spots, and some have seizures; patients with multiple café-aulait spots with seizures should be diagnosed by genetic analysis as soon as possible.

Objective:To investigate the clinical characteristics and mutation of MFSD8 gene in a family with neuronal ceroid lipofuscinosis type7 (CLN7).Methods:The clinical data of a CLN7 patient and her family from the Children′s Hospital Affiliated to Zhengzhou University in January 2018 were reviewed and analyzed. Whole exome sequencing of second-generation sequencing was used to analyze gene mutation results.Results:The proband, a five years and nine months old girl, admitted to the Children′s Hospital Affiliated to Zhengzhou University with the chief complaint of "intermittent seizures for seven months". She had the first seizure at the age of five years and two months, and different types of generalized tonic-clonic and atypical absence seizures were found. At the age of five years and nine months, she was admitted to the hospital with mild mental deterioration. She had normal motor and physical development. Ophthalmological evaluation revealed macular degeneration. The video electroencephalography revealed multifocal spikes or spike-and-wave, prominent in the anterior fronto-temporal regions. Magnetic resonance imaging (MRI) revealed cerebellar atrophy. Compound heterozygous mutations c.553 (exon 6) G>A and c.1391 (exon 13) C>T were found on her MFSD8 gene, supporting the diagnosis of CLN7. Each of her parent carried one of the mutations, and c.553 (exon 6) G>A was a new mutation. Her elder brother had the first seizure at the age of 6 years, with motor and mental deterioration as well as visual impairment. MRI revealed generalized cerebral atrophy. He had the same compound heterozygous mutations with his sister. No pathogenic mutation was found in her younger brother.Conclusions:CLN7 is a rare neurodegenerative disease, the main clinical features of which are epileptic seizures, progressive motor intelligence regression, visual loss, cranial MRI suggesting brain atrophy, and binocular macular degeneration. MFSD8 gene heterozygous mutations c.553G>A (p.V185I) and c.1391C>T (p.A464V) are the genetic etiology of this proband.

Objective:To explore the effect of parental rearing patterns and their consistency on the emotional and behavioral problems of preschool children.Methods:From October to November 2017, 27 987 children aged 3 to 6 years old from 109 kindergartens in 11 cities of Hubei, Anhui and Jiangsu Provinces were selected by using the cluster sampling method. A total of 27 200 valid questionnaires which were completed by subjects' parents were collected. The emotional and behavioral problems of preschool children were collected by "strengths and difficulties questionnaire" and the parental rearing patterns were evaluated by the "Parental Behavior Scale". The differences in emotional and behavioral abnormality rates of preschool children with different characteristics were analyzed; with emotional and behavioral problems as dependent variables and parental support/participation and compulsion/hostility as independent variables, the multivariate logistic regression model was used to analyze the effect of parental rearing patterns and their consistency on the emotional and behavioral problems of preschool children.Results:The age of children was (4.35±0.96) years old, and 51.4% of children were 13 975 males. There were 24 634 (90.6%) urban children and 17 916 (65.9%) only children. Both parents with strong support/participation accounted for 14.9%, and those with poor support/participation accounted for 11.9%; both parents with strong compulsion/hostility accounted for 15.2%, and those with low compulsion/hostility accounted for 11.3%. The rates of emotional symptoms, conduct behavior, hyperactive behavior, peer interaction, total difficulty score, and abnormal prosocial behavior of preschool children were 9.5%, 9.5%, 18.2%, 24.5%, 11.2%, and 10.2%, respectively. The multivariate logistic regression model analysis showed that after adjusting for gender, only child, living area, family economic status, mother′s age and education level, father′s education level, and other factors, compared with fathers/mothers with strong support/participation and low compulsion/hostility and parents with strong support/participation and low compulsion/hostility, preschool children who had fathers/mothers with poor support/participation and strong compulsion/hostility or parents with poor support/participation and strong compulsion/hostility were more likely to have emotional symptoms, conduct behavior, hyperactive behavior, peer interaction, total difficulty score, and abnormal prosocial behavior ( P<0.05). Conclusions:Parental rearing patterns and their consistency are related to the emotional and behavioral problems of preschool children.