Family report of Wolf-Hirschhorn syndrome in twins / 中华神经科杂志

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

Pedigree study and analysis of ATP7A gene variants in three children with Menkes disease / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for three children with Menkes disease.@*METHODS@#The patients were subjected to next-generation sequencing (NGS) to detect potential variants of the ATP7A gene. Suspected variants were verified by Sanger sequencing of their family members and 200 healthy individuals. Multiplex ligation-dependent probe amplification (MLPA) was also carried out to detect potential deletions in their family members and 20 healthy individuals.@*RESULTS@#Variants of the ATP7A gene were detected in all of the three families, including a novel c.1465A>T nonsense variant in family 1, a novel c.3039_3043del frame-shifting variant in family 2, and deletion of exons 3 to 23 in family 3, which was reported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.1465A>T and c.3039_3043del variants of ATP7A gene were predicted to be likely pathogenic (PVS1+PM2).@*CONCLUSION@#Variants of the ATP7A gene may underlay the Menkes disease in the three children. Above findings have facilitated clinical diagnosis and enriched the spectrum of genetic variants of Menkes disease.

Relationship between mutation characteristics of SCN1A gene in Dravet syndrome and its clinical phenotype and drug efficacy / 中华实用儿科临床杂志

Objective@#To explore the relationship between different mutation characteristics and clinical phenotype of children with Dravet syndrome (DS) with SCN1A gene mutation, and to summarize the drug efficacy.@*Methods@#The clinical data of children diagnosed as DS from the Department of Pediatrics Neurology, the Third Affi-liated Hospital of Zhengzhou University from January 2014 to May 2018 were collected.The peripheral blood DNA of the children was detected by adopting next generation sequencing for epilepsy-related gene-panel, while the parents′ were screened by using Sanger sequencing for family verification.Multiple ligation-dependent probe amplification technology was used to detect large fragment variation of SCN1A gene if the mutations of the children were negative.The Gesell scale and cavity Wechsler intelligence scale for children(C-WISC) were used to evaluate the intelligence of children.@*Results@#A total of 50 cases of DS were collected, 38 cases of them were positive for SCN1A mutation, and the mutation rate was 76.0%(38/50 cases), of which, the missense mutation[50.0%(19/38 cases)] and frameshift mutation[28.9%(11/38 cases)] were dominant.The average onset age of 50 patients was 6 months, of which onset of seizures was triggered by fever(temperature>37.5 ℃) in 68.0%(34/50 cases)of children, the history of seizures in hot baths was found in 60.0%(30/50 cases) of children, status epilepticus was found in 74.0%(37/50 cases), cluster-like episodes was found in 80.0%(40/50 cases), ≥2 seizure types was found in 92.0%(46/50 cases). Mental retarda-tion was found in most of the children, of which 30.0% (15/50 cases) were mild mental retardation, 38.0% (19/50 cases) were moderate mental retardation, 14.0% (7/50 cases)were severe intelligence retardation.Interictal abnormalities of electroencephalogram(EEG) before 1 year old was found in 24.0%(12/50 cases), and the average age of EEG abnormalities was 30.12 months old; the top three drug efficacy rates were 70.0% (28/40 cases) of Topiramate, 48.0% (24/50 cases) of Sodium Valproate, 45.7% (16/35 cases) Clonazepam or Clobazam.The time of onset of myoclonus and atypical absence of the truncation mutation group was earlier than that of the missense mutation group(14.75 months vs.21.20 months; 16.82 months vs.26.00 months), and the difference was statistically significant(P<0.05). The proportion of clustered episodes in the truncation mutation group was higher than that in the missense mutation group [94.7%(18/19 cases)vs.63.2%(12/19 cases)], and the difference was statistically significant (P<0.05). There was no significant correlation between the SCN1A gene mutation (type and position) and age of onset, type of seizure, proportion of convulsion persistence, the mental development or abnormal proportion of EEG and seizure frequency before 1 year old(all P>0.05).@*Conclusions@#The SCN1A gene mutation rate is high in children with DS, and the SCN1A gene mutation characteristics has a certain correlation with DS clinical phenotype.Topiramate is the most effective drug among children with DS.

Relationship between mutation characteristics of SCN1A gene in Dravet syndrome and its clinical phenotype and drug efficacy / 中华实用儿科临床杂志

Objective To explore the relationship between different mutation characteristics and clinical phenotype of children with Dravet syndrome (DS) with SCN1A gene mutation,and to summarize the drug efficacy.Methods The clinical data of children diagnosed as DS from the Department of Pediatrics Neurology,the Third Affiliated Hospital of Zhengzhou University from January 2014 to May 2018 were collected.The peripheral blood DNA of the children was detected by adopting next generation sequencing for epilepsy-related gene-panel,while the parents' were screened by using Sanger sequencing for family verification.Multiple ligation-dependent probe amplification technology was used to detect large fragment variation of SCN1A gene if the mutations of the children were negative.The Gesell scale and cavity Wechsler intelligence scale for children(C-WISC) were used to evaluate the intelligence of children.Results A total of 50 cases of DS were collected,38 cases of them were positive for SCN1A mutation,and the mutation rate was 76.0％ (38/50 cases),of which,the missense mutation[50.0％ (19/38 cases)] and frameshift mutation[28.9％ (11/38 cases)] were dominant.The average onset age of 50 patients was 6 months,of which onset of seizures was triggered by fever(temperature ＞ 37.5 ℃) in 68.0％ (34/50 cases)of children,the history of seizures in hot baths was found in 60.0％ (30/50 cases) of children,status epilepticus was found in 74.0％ (37/50 cases),cluster-like episodes was found in 80.0％ (40/50 cases),≥2 seizure types was found in 92.0％ (46/50 cases).Mental retardation was found in most of the children,of which 30.0％ (15/50 cases) were mild mental retardation,38.0％ (19/50 cases) were moderate mental retardation,14.0％ (7/50 cases)were severe intelligence retardation.Interictal abnormalities of electroencephalogram(EEG) before 1 year old was found in 24.0％ (12/50 cases),and the average age of EEG abnormalities was 30.12 months old;the top three drug efficacy rates were 70.0％ (28/40 cases) of Topiramate,48.0％ (24/50 cases) of Sodium Valproate,45.7％ (16/35 cases) Clonazepam or Clobazam.The time of onset of myoclonus and atypical absence of the truncation mutation group was earlier than that of the missense mutation group(14.75 months vs.21.20 months;16.82 months vs.26.00 months),and the difference was statistically significant (P ＜ 0.05).The proportion of clustered episodes in the truncation mutation group was higher than that in the missense mutation group [94.7％ (18/19 cases)vs.63.2％ (12/19 cases)],and the difference was statistically significant (P ＜0.05).There was no significant correlation between the SCN1A gene mutation (type and position) and age of onset,type of seizure,proportion of convulsion persistence,the mental development or abnormal proportion of EEG and seizure frequency before 1 year old(all P ＞ 0.05).Conclusions The SCN1A gene mutation rate is high in children with DS,and the SCN1A gene mutation characteristics has a certain correlation with DS clinical phenotype.Topiramate is the most effective drug among children with DS.

Expression of nucleotide-binding oligomerization domain-like receptor protein 3 inflammatory corpuscles in epileptic model and the effect of melatonin on its expression / 中华实用儿科临床杂志

Objective To observe the expression of nucleotide-binding oligomerization domain-like recep-tor protein 3(NLRP3)inflammasome in epilepsy model,and to explore the neuroprotective effect of melatonin. Methods SD rats aged 21-30 d were randomly divided into the control group(48 rats),the epilepsy group(48 rats)and the melatonin group(48 rats),and each group was subdivided into 4 subgroups according to the time points of 24 h,48 h, 72 h,and 7 d,with 12 SD rats in each subgroup. Fluorescence quantitative polymerase chain reaction and immunohisto-chemical technique were used to analyze the expressions of NLRP3,Caspase-1 and interleukin(IL)-1β in hippocam-pus areas of rats at different points of time after seizures were induced,and their behavior changes were observed. Results The number of NLRP3-positive cells in the epileptic group increased,and reached the peak at 72 h. At 24 h,48 h,72 h,7 d,the number of NLRP3-positive cells in the epilepsy group(14. 20 ± 1. 64,23. 60 ± 1. 14,31. 20 ± 1. 30,25. 40 ± 2. 07)was significantly increased compared with those of the melatonin group(10. 60 ± 0. 89,17. 80 ± 1. 48,24. 00 ± 0. 71,20. 20 ± 1. 92)and the control group(2. 60 ± 0. 89,2. 40 ± 1. 14,2. 40 ± 1. 14,2. 40 ± 0. 55),and the differences were significant(F＝122. 977,375. 125,962. 743,262. 916,all P＜0. 05). The NLRP3 mRNA relative expressions in the epilepsy group (2. 57 ± 0. 12,3. 34 ± 0. 10,4. 84 ± 0. 19,3. 55 ± 0. 13)were significantly increased compared with those of the melatonin group (2. 03 ± 0. 08,2. 71 ± 0. 08,4. 03 ± 0. 14,2. 48 ± 0. 18)and the control group(1. 07 ± 0. 13,1. 08 ± 0. 15,1. 08 ± 0. 23,1. 07 ± 0. 18),and the differences were significant (F ＝422. 386, 1 154. 957,1 132. 112,512. 149,all P ＜0. 05);the Caspase -1 mRNA relative expressions in the epilepsy group (2. 47 ± 0. 07,3. 05 ± 0. 15,4. 39 ± 0. 18,3. 14 ± 0. 11)were significantly increased compared with those of melatonin group(1. 85 ± 0. 07,2. 49 ± 0. 08,3. 60 ± 0. 12,2. 15 ± 0. 12)and the control group (0. 98 ± 0. 25,0. 99 ± 0. 15,0. 98 ± 0. 23,0. 99 ± 0. 18),and the differences were significant(F ＝620. 099,580. 796,1 125. 225,645. 082,all P ＜0. 05);the IL-1β mRNA relative expressions in epilepsy group (2. 32 ± 0. 15,2. 90 ± 0. 18,4. 18 ± 0. 16,2. 74 ± 0. 07)were significantly increased compared with those of the melatonin group (1. 78 ± 0. 09,2. 35 ± 0. 11,3. 24 ± 0. 13,1. 78 ± 0. 16)and the control group(0. 97 ± 0. 13,0. 99 ± 0. 15,0. 97 ± 0. 23,0. 97 ± 0. 18),and the differences were significant(F＝267. 952,398. 767,1 140. 384,438. 962,all P ＜0. 05). Conclusions The NLRP3 inflamma-somes are activated in rat hippocampus with epilepsy induced by lithium-pilocarpine. NLRP3 inflammasome mediated inflammatory response probably involved in the pathogenesis of epilepsy. The melatonin may play a neuroprotective role by inhibiting expression of NLRP3 inflammasome.

Comparison of efficacy of adrenocorticotrophic hormone and methylprednisolone on rat models of infantile spasm / 中华实用儿科临床杂志

Objective To compare the efficacy of adrenocorticotrophic hormone (ACTH) and methylprednisolone on the rat models of infantile spasms (IS).Methods The SD rats on postnatal 10 day (P10) were divided into blank group (n =18),control group (n =18) and model group (n =110) according to the random number table method.The rats of model group were prepared by adopting prenatal stress exposure and N-methyl-D aspartate (NMDA) injection.In the model group,after inducing epileptic seizures,the rats were divided into different groups (18 rats in each group) according to the random number table method as following:model group Ⅰ (subcutaneous injection ofACTH,50 IU/kg,at P10:14:00,21:00;P11,P12:7:00,14:00,21:00;P13:7:00),model group Ⅱ (subcutaneous injection of 9 g/L saline),model group Ⅲ (intraperitoneal injection of methylprednisolone,60 mg/kg,at P11,P12,P13:9:00,once per day),model group Ⅳ (intraperitoneal injection of 9 g/L saline) and model group Ⅴ (positive control group,with no drug or saline injection).Three days later,epilepsy was induced again,and the rats of model group were intraperitoneally injected with NMDA (12 mg/kg) at P13 (10:00).The rats of control group were injected intraperitoneally with same volume of 9 g/L saline,but the rats of blank group were not treated.Behaviors of rats with epilepsy seizures were observed and epilepsy scores were given.The expression of corticotropin-releasing hormone (CRH) in the hypothalamus of each group was detected by using immunohistochemistry and fluorescence quantitative polymerase chain reaction.The learning and memorizing capacity of the rats were measured by Y-maze experiment.Results There was no death in the model group after the onset of seizure.In the model group Ⅰ,13 cases were attacked(72.22％),and 14 cases were attacked in the model group Ⅲ (78.78％).The level of attack was decreased.The buckling state was not observed in model group and Ⅲ,but the latency period of epilepsy was prolonged and the epilepsy scores were significantly decreased.There were no significant differences of onset latency [(2 369.38 ± 628.70) s vs.(1 922.93 ± 462.36) s] and epilepsy score [(2.15 ± 1.14) scores vs.(2.07 ± 0.83) scores] between the 2 groups (all P ＞ 0.005).The rats of model group Ⅱ,Ⅳ,Ⅴ were all attacked completely and presented buckling state.There was no onset or death in blank group and control group.The number of CRH positive cells and CRH mRNA relative expression of each model group were higher than those in the blank group and control group.The number of CRH positive cells and CRH mRNA expression of model group Ⅰ and Ⅲ were lower than those in model group Ⅱ,Ⅳand Ⅴ,and the differences were significant (all P ＜ 0.002 4).There was no significant difference in the number of CRH-positive cells(39.12 ± 5.98 vs.41.48 ± 7.61) and CRH mRNA relative expression (1.92 ± 0.16 vs.2.06 ± 0.39) between model group Ⅰ and Ⅲ (all P ＞ 0.002 4).No significant difference was found between blank group and control group,or among model group Ⅱ,Ⅳ and Ⅴ (all P ＞ 0.002 4).There were no significant differences in the learning capacity among all groups (F =2.196,P ＞ 0.002 4).The correct response rate after 24 hours of the model group was lower than the blank group and control group,and ACTH and methylprednisolone pretreatment did not influence the memorizing capacity (P ＞ 0.002 4).Conclusion The effect of pretreatment of ACTH is similar to that of methylprednisolone in the rat model of IS.

The curative effect analysis on central retinal artery occlusion treated by compound anisodine / 中国基层医药

Objective Compare the difference on vision,vision field between treating on central retinal artery with compound anisodine retrobulbar injection associate with emporat artery side injection and emporal artery side injection simply.Estimate the curative effect of the two ways on the disease.Methods Observe the patients'vision,vison field and cross-check,analyze the results who have central retinal artery and there are 20 who treated by compound anisodine retrobulbar injection associate with emporal artery side injection together with 20 who treated by emporal artery side injection purely.Results The therapeutics that is compound anisodine retrobulbar injection associate with emporal artery side injection is excellence to 10,effective to 6 and ineffective to 4;the therapeutics that is arter3,side injection purely is excellence to 5,effective to 5 and ineffective to 10.The two therapeuticses has significant difference on improving vision and ameliorating vision field.Conclusion It's quite effective to treat central retinal artery occlusion by compound anisodine retrobulbar injection associate with emporal artery side injection.

Clinical analysis of surgical treatment to 26 cases Orbital Blowout Fracture / 中国基层医药

Objective To estimate the effection of orbital blowout fracture when Medpor was implanted to restore it. Methods The plastic operations on 15 patients with orbital blowout fracture were reviewed and studied. Results On discharge from the hospital, function and outline form was improved greatly in all cases. Conclusion Early diagnosis, early treatment and early movement training after surgery were emphasized. Medpor is one of the preferred material on reparing orbital blowout fracture.