Background

Epileptic encephalopathies (EE) are characterized by recurrent clinical seizures or prominent interictal epileptiform discharges manifesting with impaired cognitive, sensory, and motor development. Early-onset EE typically have onset during the first 2 years of life. Despite baseline (clinical ± neuroimaging ± metabolic ± electrophysiology) evaluation, definite diagnosis may be elusive in a proportion of children with EE. These are presumed to be of genetic origin. Next generation sequencing (NGS) has proven to be of value as a diagnostic tool in clinical practice. Here we present the data of patients who underwent NGS for Early-Onset EE in a tertiary-care centre in India.

Objective

To determine the diagnostic yield of NGS for Early-Onset EE

Methods

We performed retrospective analysis of 21 children who underwent NGS between Jan-2018 to Jun-2018 for previously unexplained Early-onset EE.

Results

Pathogenic mutations were identified in 13/21 (61.9%) patients and included: SCN1A (n=2), KCNQ2 (n=2), DHDDS (n=2), GRIN2B (n=1), STXBP1 (n=1), PC (N=1), POLG2 (n=1), SPTAN (n=1), PCDH19 (n=1) and SCN2A (n=1). Variants of unknown significance were identified in 4 patients (SLC9A6 (n=2), CACNA1A (n=1), and SPTAN1 (n=1)). The impact of NGS result on clinical management included: reproductive planning (n=20), changes in disease monitoring strategies (n=12), assessment of asymptomatic sibling (n=6), investigation for systemic involvement (n=2), and medication discontinuation (n=3) or initiation (n=5).

Conclusion

The high diagnostic yield of NGS supports its use Early-Onset EE. The definitive diagnosis may impact medical management, prognostication and reproductive planning.