Clinical features and genome-wide copy number variation analysis in 60 children with early-onset epileptic encephalopathies of unknown cause

Abstract:

Objective To study the clinical features of early-onset epileptic encephalopathies (EEEs) of unknowncause, and to identify pathogenic microdeletion/microduplication of EEEs by genome-wide analysis of copy numbervariations (CNVs). Methods The clinical data of 60 children diagnosed with unexplained EEEs between July 2012 and April 2013 were obtained and analyzed. Specimens were collected from the selected children and their parents.Single nucleotide polymorphism array was used to detect genome-wide CNVs, and fluorescence in situ hybridizationwas performed to verify the results and analyze the source of the parents, further to identify suspected pathogenic CNVsof EEEs. Results Among the 60 children with unexplained EEEs, 34 were diagnosed with West syndrome, 3 withOhtahara syndrome, 3 with Dravet syndrome, and 20 with unclassified EEEs. In total, 77% of the patients were associatedwith moderate to severe mental retardation. Head imaging test implied that 35% of the patients had brain dysplasiaor astrophy. Among 54 patients, 17% showed microcephalus. After treatment, 28 patients had clinical seizures undercontrol, 16 out of control, 5 dead, and 1 lost to follow-up. Genome-wide analysis of CNVs showed that 7 pathogenic orsuspected pathogenic CNVs were present in 5 patients. Conclusions EEEs of unknown cause are associated with highphenotypic heterogeneity and poor prognosis. Genome-wide CNVs analysis can demonstrate pathogenic or suspectedpathogenic CNVs. This research expands the gene bank of EEEs and improves the understanding about possible etiologyof unexplained EEEs. The results provide a reference for genetic counseling regarding reproduction in the patient'sfamily.