The data of a child with early-onset epileptic encephalopathy in Qilu Children′s Hospital of Shandong University in February 2020 were analyzed retrospectively.The child was a 4-month-old girl, who was admitted to the hospital because of " repeated convulsions for 4 months and feeding difficulty for 1 month" at the age of 4 months.The patient suffered from epilepsy 1 day after birth, and the epilepsy type was tonic seizures.Severe developmental retardation was observed in the patient.Electroencephalogram showed multifocal discharge, which then turned to hypsarrhythmia.The cranial imaging was negative.Feeding difficulty occurred at the age of 3 months.The genetic testing revealed a de novo heterozygous missense mutation in the FGF12 gene (Arg114His). Various antiepileptic drugs and ketogenic diet were ineffective.There was no attack in 2 months after adding Phenytoin.The child could eat on her own after seizure control, but there was no progress in intellectual and motor development.Mutations in the FGF12 gene lead to poor prognosis of early-onset epileptic encephalopathy, and the seizures are difficult to control.Sodium ion channel blockers such as Phenytoin should be used as soon as possible.

OBJECTIVE: To investigate the clinical and genetic features of a Chinese girl featuring mental retardation, intellectual disability, language development delay and epilepsy. METHODS: G-banded chromosomal karyotyping was carried out for the child. Genomic DNA of the patient and her parents was extracted and subjected to high-throughput sequencing. The results were analyzed with bioinformatic tools and validated by Sanger sequencing. RESULTS: The karyotype of the child was ascertained as 46,XX. Sequencing result showed that she has carried a de novo heterozygous c.1861C>T (p.R621X) variant of the SYNGAP1 gene. CONCLUSION The nonsense variant c.1861C>T (p.R621X) of the SYNGAP1 gene probably underlies the disease in this child. Above result has enabled genetic diagnosis and counseling for her family.

OBJECTIVE: To explore the genetic basis for a Chinese boy featuring developmental delay and epilepsy. METHODS: Clinical data of the patient was collected. Genomic DNA of the patient and his parents was extracted and subjected to high-throughput sequencing. Pathogenicity of the variant was predicted and validated. RESULTS: Sequencing results showed that the patient has carried a de novo c.1470delA (p.V491Ffs*6) variant of the UBE3A gene, which was predicted to be pathogenic. CONCLUSION The frameshift variant c.1470delA (p.V491Ffs*6) probably underlay the disorders in this child.

Clinical data of a case with early-onset epileptic encephalopathy admitted in the Department of Neuroendocrinology, Jinan Children′s Hospital in April 2020 were retrospectively analyzed.A 1-month-old male patient was hospitalized for convulsion for 4 days.The child had repeated seizures in the form of tonic and tonic-spasm seizures, accompanied by feeding difficulties, slow weight gain, and overall developmental delay.Electroencephalogram showed multifocal discharge, atypical hypsarrhythmia, and brain magnetic resonance imaging showed delayed myelination.The whole exome sequencing showed compound heterozygous mutation of the WWOX gene.Topiramate, Levetiracetam and Valporate were ineffective to this case.Genetic testing should be performed timely in patients with early-onset epileptic encephalopathy and overall developmental delay to make a clear etiology and prognosis, thus guiding prenatal diagnostics and genetic counseling.

A retrospective analysis was performed on the clinical data of a case of intellectual developmental disorders with dysmorphic facies and behavioral abnormalities admitted in the Department of Neurology and Endocrinology, Children′s Hospital Affiliated to Shandong University in February 2020.The proband was a 3 years and 6 months old boy, who was hospitalized because of " convulsions for more than 1 year" . Physical examination revealed facial deformities.Gesell developmental schedule showed that adaptive and gross motor behavior development was severely retarded, and fine motor, language and personal-social behavior development was moderately retarded.Brain magnetic resonance imaging suggested schizencephaly.Electroencephalogram results indicated extensive discharges mainly in bilateral anterior head areas, and one myoclonic seizure was detected.Gene detection results disclosed the pathogenic variation of the proband, which was a heterozygote mutation (c.2480_2484del) in FBXO11 gene.High-throughput sequencing technology increases the possibility of identifying potential genetic mutations as the cause of disease.Patients with recurrent seizures, multi-malformation and general developmental delays should undergo gene detection in time to clarify the etiology.This technique can guide prenatal diagnosis and genetic counseling.

At present，the infection disease caused by novel coronavirus （2019-nCoV） is very serious. In addition to mainly affecting the lungs，the virus can also affect the nervous system，digestive system，urinary system，and blood system，which is highly infectious and generally susceptible to people. The main source of infection is the new coronavirus infection of patients，asymptomatic infected people may also become the source of infection. During the EEG recording，medical staff，accompanying family members，other patients and examination rooms may be threatened by the virus infection，In order to remind the relevant staff to perform effective protection and avoid the risk of infection in similar incidents in the future. We summarize the current diagnosis and treatment of clinical diseases caused by 2019-nCoV and related research progress，so as to make the staff of epilepsy center （or EEG room） familiar with the relevant prevention，and treatment process，diagnosis and treatment indications and control programs.

OBJECTIVE: To explore the genetic etiology of a child with Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR). METHODS: A child who was admitted to the Children's Hospital of Shandong University on July 9, 2021 due to repeated convulsions for 2 months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 1-year-and-7-month-old male, had presented with epilepsy and global developmental delay. Serological testing revealed that he has low serum magnesium. Genetic testing showed that the child has harbored a heterozygous c.1448delT (p.Val483GlyfsTer29) variant of the CNNM2 gene, which was de novo in origin. The variant has caused substitution of the Valine at position 483 by Glycine and formation of a termination codon after 29 amino acids at downstream. As predicted by Swiss-Model online software, the variant may alter the protein structure, resulting in a truncation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1448delT (p.Val483GlyfsTer29) was predicted as a pathogenic variant (PVS1+PS2+PM2_Supporting+PP4). CONCLUSION The heterozygous c.1448delT variant of the CNNM2 gene probably underlay the HSMR in this child. Above finding has enriched the phenotype-genotype spectrum of the CNNM2 gene.
Humans ; Male ; Cation Transport Proteins ; Computational Biology ; Ethnicity ; Intellectual Disability/genetics* ; Magnesium ; Mutation ; Seizures/genetics* ; Infant

Objective:To investigate the clinical and genetic characteristics of developmental and epileptic encephalopathy (DEE) caused by SLC1A2 gene mutations. Methods:The clinical manifestations, auxiliary examination results, and genetic testing results of a patient with DEE caused by SLC1A2 gene mutations who was treated at Epilepsy Center, Children's Hospital Affiliated to Shandong University on February 6, 2021 were summarized. Cases of SLC1A2 gene mutations were searched using keywords " SLC1A2" and "developmental and epileptic encephalopathy" in CNKI, Wanfang, and PubMed databases, retrieving literature published from the establishment of these databases to September 2024. Bioinformatics analysis was performed; the clinical and genetic characteristics of DEE caused by SLC1A2 gene mutations were summarized. Results:The main manifestations of the patient were rhythmic shaking of the right upper limb or focal motor seizures of bilateral upper limbs, or focal spasm of right upper limb (elevation for once). Ictal electroencephalogram showed 2-3 Hz polymorphic slow waves in the left central area, parietal area and central midline area, affecting the opposite side, or spike rhythm with decreased frequency in the right frontal area, central area and midline area, or polymorphic slow waves in the left central area and central midline area. Whole-exome sequencing indicated a heterozygous de novo mutation in the SLC1A2 gene: c.254T>G/p.Leu85Arg. A total of 7 patients with DEE caused by SLC1A2 gene mutations were retrieved from 5 related literature. All 8 patients (including the patient in our hospital) presented with epileptic seizure, developmental delay, and abnormal EEG; all of them were sporadic cases with de novo heterozygous missense mutations of SLC1A2 gene. Bioinformatics analysis showed that the 4 amino acid residues Gly82, Leu85, Pro289, and Pro333 in the 8 patients were located in the intolerance region of SLC1A2 gene encoding glutamate transporter protein 2 (EAAT2). The 5 amino acid mutations (Leu85Arg, Leu85Pro, Gly82Arg, Pro333Ser, Pro289Arg) in the 8 patients all led to significant changes in number and binding of hydrogen bonds between amino acid residues in EAAT2; except for Gly82Arg mutation, the other 4 mutations could obviously reduce the structural stability of EAAT2. Conclusion:De novo heterozygous missense mutations in SLC1A2 gene can lead to DEE, characterized by developmental delay, EEG abnormalities, and epileptic seizure; these mutations are typically located in critical regions of EAAT2, potentially resulting in reduced protein structural stability.

OBJECTIVE: To detect pathogenic mutation of DOCK6 gene in a patient with convulsive seizure and refractory epilepsy. METHODS: CytoScan HD-Array and next generation sequencing were used to detect the potential mutation in the patient. RESULTS: The proband has carried compound heterozygous mutations of c.188C>T (p.Arg63Gln) and c.5374C>T (p.Glu1792Lys) of the DOCK6 gene, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis indicated that the two amino acids are highly conserved. Based on the ACMG guidelines, the c.188C>T mutation was predicted to be likely pathogenic, while the c.5374C>T mutation was of uncertain significance. CONCLUSION The compound heterozygous mutations of c.188C>T (p.Arg63Gln) and c.5374C>T (p.Glu1792Lys) of the DOCK6 gene probably underlie the disease in this patient.
Child ; Diabetes Mellitus, Type 2 ; Ectodermal Dysplasia ; genetics ; Guanine Nucleotide Exchange Factors ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Mutation ; Pedigree ; Scalp Dermatoses ; congenital ; genetics