| Background: Epileptic encephalopathy is a severe brain disease of progressive psychomotor dysfunction caused by epilepsy or epileptic discharge,it is most common in infancy.The main features of epileptic encephalopathy are: uncontrollable epilepsy,severe electroencephalographic abnormalities,developmental delay or regression,and mental retardation.Excluding perinatal brain injury,brain trauma,brain tumors,central nervous system infections,metabolic diseases,chromosomal diseases,and monogenic diseases in identified phenotype,the etiology of one third infants still unknown.Infantile epileptic encephalopathy includes early myoclonic encephalopathy,Ohtahara syndrome,West syndrome,Dravet syndrome,maligant migrating partial seizures in infancy,and non-syndrome infantile epileptic encephalopathy that are not yet clearly categorized.The onset of infantile epileptic encephalopathy is early,and frequent epileptic seizures can cause severe damage to early brain development.At present,the common treatment methods for infantile epileptic encephalopathy include anti-epileptic drugs,hormone,ketogenic diet,and surgical treatment,but the effectiveness of them is poor which resulting in high mortality and disability.At present,there are more than 70 kinds of epileptic encephalopathy-related pathogenic genes discovered at home and abroad,among which there are more than 50 mutated genes related to early infantile epileptic encephalopathy.The genetic etiology is beneficial for genetic counseling,prognostic evaluation,prenatal diagnosis and prenatal intervention,thereby reducing the birth rate of unhealthy infants.By understanding the genotype-phenotype relationship,we can further make genetic diagnosis and provide evidence for classification.It's helpful to select appropriate anti-epileptic drugs and treatment programs combining the clinical features,classification diagnosis and types of gene mutation.Objective: To analyze the clinical and genetic mutation features of infants with infantile epileptic encephalopathy and offer help for the classification diagnosis,reasonable treatment,genetic counseling and prognosis assessment of these infants.Method:Clinical data of 47 infants with unexplained infantile epileptic encephalopathy treated in the pediatrics department of Fuzhou General Hospital from January 2014 to January 2017 were collected.The blood samples of these infants and their parents were collected,and 4000 gene mutations in monogenic disease of all cases(Trios)were analyzed by the next-generation sequencing technology.Moreover,analyze the clinical and gene mutation features of these infants.Results: The age of onset in 47 infants with unexplained infantile epileptic encephalopathy was mostly within 3 months after birth(22 cases,46.81%),followed by7-9 months(15 cases,31.91%).35 epilepsy syndrome infants were diagnosed: 15 DS(31.91%),12 WS(25.53%),4 EME(8.51%),and 4 OS(8.51%).No MMPS was found.12 non-syndrome infantile epileptic encephalopathy could not be classified(25.53%).2DS infants appeared tonic seizure during the course of disease,which is a rare seizure form of DS.All 47 infants were treated with anti-epileptic drugs,mainly drug combination.5 infants(10.64%)achieved epilepsy control,18(38.83%)were effective,and 24 were ineffective.(51.06%).In the follow-up of the prognosis,1 infant died and 1infant lost.All survival infants had different levels of mental retardation.Among 22 infants with early onset of epileptic encephalopathy within 3 months,12 with severe ID(54.55%),4 with extremely severe ID(18.18%).Among 25 infants with onset of epileptic encephalopathy after 3 months,5 with severe ID(20.00%),and 1 with extremely severe ID(4.00%).Results of gene mutation detection: Gene mutations were detected from 23 infants,the positive rate was 48.94%(23/47).12 infants were de nove mutation,and 11 infants had heterozygous mutations from their father or mother.Among 23 positive infants,17 had epileptic encephalopathy-related gene mutations,accounting for 73.91%,2 infants had gene mutations related to metabolism,accounting for 8.70%,2 infants had gene mutations related to brain structural abnormalities,accounting for 8.70%,2 infants had gene mutations related to mental retardation,accounting for 8.70%.Among the 17 epileptic encephalopathy-related gene mutations,14 were ion channel gene mutations(82.35%),and 3 were non-ionic channel gene mutations(17.65%).Among 22 infants of early-onset of infantile epileptic encephalopathy within 3 months,12 infants were detected with gene mutation related to early infantile epileptic encephalopathy,accounting for 54.55%.The gene mutation of 2 DS with tonic seizures were SCN1 A missense mutations.Conclusions: 1.The highest incidence age of unexplained infantile epileptic encephalopathy is within 3 months after birth,followed by 7-9 months.The incidence of DS is the highest,followed by WS.2.It is difficult to treat unexplained infantile epileptic encephalopathy,especially the infants within 3 months after birth,and the prognosis is poor.3.Infants with DS may appear rare form of tonic seizure.4.Most gene mutations of unexplained infantile epileptic encephalopathy are related to epileptic encephalopathy,and the types of gene mutation mainly are ion channel gene mutation.5.Early-onset epileptic encephalopathy related gene mutations were the main cause of infantile epileptic encephalopathy within 3 months.6.Gene mutations related to abnormal brain structure and genetic metabolism disease may be potential etiology of unexplained infantile epileptic encephalopathy,genes related to mental retardation may be the candidate mutation gene of infantile epileptic encephalopathy.7.2 DS with tonic seizure were SCN1 A gene mutation. |
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