Clinical features and genetic analysis of intellectual disability in children with epilepsy of unknown causes

Abstract

Objective To explore the clinical features, genetic causes and prognosis of intellectual disability with epilepsy(ID-E) in children. Methods The data of unknown causes of ID-E children(n=40) who were identified in Department of Pediatrics, Xiangya Hospital of Central South University from March 2015 to March 2016 were respectively analyzed, and follow-up studies were performed to investigate the epilepsy control and intellectual deve-lopment. Results Forty unexplained ID-E included 25(62.5%) male, and 34(85.0%) cases were severe intellectual disability patients.The onset age of epilepsy was 0.16 to 8.00 years old, median age was 1.5 years old.Twenty cases (50.0%) had slow electroencephalogram background, and 22 cases(55.0%) had focal spikes.Ten cases(25.0%) had abnormal cranial images, with brain dysplasia or atrophy.Follow-up lasted from 0.58 to 1.58 years, and 19 cases (47.5%) had seizure control.Twenty-five cases (62.5%) had used at least 2 anti-epilepsy drugs during follow-up, and 19 cases (47.5%) had drug refractory epilepsy.Improvement of mental or motor development in epilepsy controlled group and the uncontrolled group were 12 cases (63.2%) and 2 cases (9.5%). There were separately 8 cases(8/40 cases, 20.0%) and 3 cases(3/16 cases, 18.8%) diagnosed respectively by whole genome-wide analysis of copy number variants(CNVs) and gene-panel whose CNVs test findings were negative. Conclusions ID-E patients of unknown causes have the following clinical features: they were mostly found in male patients with severe intellectual disability, and drug refractory epilepsy patients have rather high percentage; well controlling of epilepsy is useful for improvement of mental and motor development.Genetic analysis is significant for control and prognosis of ID-E patients, and genome-wide CNVs have high positive rates which can be used as first-tier test to detect genetic etiology of ID-E of unknown cause. Key words: Intellectual disability; Epilepsy; Genetic test