Clinical features and genetic analysis of early-onset epileptic encephalopathy with pachygyria-lissencephaly / 中华实用儿科临床杂志

ABSTRACT

Objective To study the clinical phenotype and prognosis of children diagnosed with early-onset epileptic encephalopathy (EOEE) and pachygyria-lissencephaly,and to explore the potential genetic factors.Methods The clinical data of 65 children between December 2005 and December 2016 was obtained and analyzed.And the whole exome sequencing was analyzed by using second generation sequencing technology.Results Among 65 children,17 cases (26.1％) were diagnosed as lissencephaly,34 cases (52.3 ％) were pachygyria,and 14 cases (62.6％)were pachygyria with lissencephaly.Thirteen cases (20.0％) were infantile spasms,9 cases (13.8％) were ohtahara syndrome,3 cases (4.6％) were early myoclonic epileptic encephalopathy,and 40 cases (61.6％) were non-symptomatic EOEE.Six cases (6/65 cases,9.2％) were associated with dyskinesia,of whom 3 cases showed dystonia,2 cases of limb tremor,1 case of dancing-like movements.Electroencephalophalogram (EEG) showed serious multifocal discharge,40 cases had massive multifocal discharge.Brain images showed that simple pachygyria was more common (34/65 cases,52.3 ％).Among them,focal pachygyria was more common (25/34 cases,73.5 ％),mostly involving in the frontoparietal lobe (11/25 cases,44.0％).Copy number variations and whole exon sequencing were performed on 61 patients.Copy number variation was detected in 1 patient.There were 2 cases of lissencephaly-1/platelet-activating factor acetylhydrolase isoform 1B (LIS1/PAFAH1B1) mutation,1 case of syntaxin-blinding protein 1 (STXBP1)mutation,1 case of Aristaless-related homeobox (ARX) mutation,and 1 case of dynein cytoplasmic 1 heavy chain 1(DYNC1H1) mutation.The follow-up time varied from 1 year to 8 years [(3.5 ± 1.4) years],in which 20 cases had clinical seizures under control but 45 cases out of control.Conclusion Infantile spasms and non-syndromic EOEEare more common in children diagnosed with EOEE and pachygyria-lissencephaly.A small number of cases have dyskinesia.EEG shows serious abnormalities,mostly multifocal discharge.Brain images show simple pachygyria is more common,mostly involving in the frontoparietal lobe.Common gene mutations are LIS1/PAFAH1B1,STXBP1,ARX.Gene mutations can lead to both clinical manifestations of cortical deformity and EOEE,and genetic factors play an important role in children with brain developmental deformity and epilepsy.