A Wide Spectrum of Genetic Disorders Causing Severe Childhood Epilepsy in Taiwan: A Case Series of Ultrarare Genetic Cause and Novel Mutation Analysis in a Pilot Study.

BACKGROUND

Pediatric epileptic encephalopathy and severe neurological disorders comprise a group of heterogenous diseases. We used whole-exome sequencing (WES) to identify genetic defects in pediatric patients.

METHODS

Patients with refractory seizures using ≥2 antiepileptic drugs (AEDs) receiving one AED and having neurodevelopmental regression or having severe neurological or neuromuscular disorders with unidentified causes were enrolled, of which 54 patients fulfilled the inclusion criteria, were enrolled, and underwent WES.

RESULTS

Genetic diagnoses were confirmed in 24 patients. In the seizure group, ACS1, , SZT2, , 16p13.11 microdeletion, [4p16.3p16.1(68,345-7,739,782)X1, 17q25.1q25.3(73,608,322-81,041,938)X3], and were identified. In the nonseizure group, , and were identified. Ten novel mutations were identified. The recurrent genes included , and . Male pediatric patients had a significantly higher (57% vs. 29%; < 0.05, odds ratio = 3.18) yield than their female counterparts. Seventeen genes were identified from the seizure groups, of which 82% were rare genetic etiologies for childhood seizure and did not appear recurrently in the case series.

CONCLUSIONS

Wide genetic variation was identified for severe childhood seizures by WES. WES had a high yield, particularly in male infantile patients.