Study on genetics and early diagnosis of early onset epileptic encephalopathy of unknown etiology / 中华实用儿科临床杂志

ABSTRACT

Objective:To explore the genetic etiology and the value of early diagnosis of early onset epileptic encephalopathy (EOEE) with unknown etiology.Methods:A total of 60 children with EOEE of unknown etiology were prospectively enrolled in the outpatient and inpatient departments of Fujian Provincial Hospital from January 2018 to January 2021.Peripheral blood was collected prospectively for whole-exome sequencing and copy number variation (CNV) detection to analyze the clinical characteristics and genetic sequencing results of the children.Results:Twenty-four patients with EOEE-related pathogenic or suspected pathogenic mutations were detected, including infantile spasms (10 cases), Dravet syndrome (3 cases), pyridoxine-dependent epilepsy (1 case) and ohtahara syndrome (1 case), and unknown epileptic encephalopathy (9 cases). The onset age of EOEE-related patients ranged from 1 day to 11 months (median age was 4.2 months), the treatment age ranged from 2 days to 4 years (median age was 10 months), and the age of diagnosis was controlled within 1 month after treatment.There were 20 cases (33.3%) single gene variants and 4 cases (6.7%) CNV variants.A total of 13 genes were involved: KCNQ2, SCN1A, SCN8A, CACNA1E, CDKL5, PPP3CA, PCDH19, TSC1, TSC2, ZEB2, ALDH7A1, DCX and HNRNPU.The 4 CNV abnormalities were 17p13.3 deletion, 11q23.3q25 deletion, 1q36.31-p36.33 deletion, 1q43-1q44 deletion and Xp22.33 duplication, respectively.Totally, 20 mutations were new loci reported for the first time at home and abroad; 11q23.3q25 deletion that resulted in infantile spasm was first reported at home and abroad.Infantile spasm caused by ZEB2 mutation and epileptic encephalopathy caused by PPP3CA gene were both reported for the first time in China. Conclusions:Gene and CNV are important potential causes of children suffering from EOEE.When the etiology is unclear, the combination of whole-exome sequencing and CNV sequencing technology can improve the diagnosis level of genetic etiology of children with EOEE.The early genetic detection of these children can early diagnose and accurately treat epilepsy.