Case report of intellectual developmental disorder with dysmorphic facies and behavioral abnormalities due to FBXO11 gene mutation / 中华实用儿科临床杂志

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.

Case report of intellectual developmental disorder with dysmorphic facies and behavioral abnormalities due to FBXO11 gene mutation / 中华实用儿科临床杂志

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.

Case report of early-onset epileptic encephalopathy caused by compound heterozygous mutation of the WWOX gene / 中华实用儿科临床杂志

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.

Case report of early-onset epileptic encephalopathy caused by FGF12 gene mutation / 中华实用儿科临床杂志

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.

Clinical and genetic analysis of a patient with Angelman syndrome due to a frameshift variant of UBE3A gene / 中华医学遗传学杂志

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.

A case with autosomal dominant mental retardation type 5 due to de novo SYNGAP1 variant / 中华医学遗传学杂志

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.

Analysis of DOCK6 gene mutation in a child affected with Adams-Oliver syndrome type 2 / 中华医学遗传学杂志

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.