FIGURE 4.

The protocol of SCN2A‐related developmental epileptic encephalopathy. First‐line investigation: plasma amino acids, homocysteine, urine organic acids, acylcarnitine profile, total and free carnitine, urine GAA and creatine, urine alpha‐AASA, aCGH, and brain MRI. Second/Third‐line investigations: targeted next generation sequencing panels of developmental epileptic encephalopathy genes or whole‐exome sequencing. Fourth‐line investigations: muscle biopsy, skin biopsy, and CSF metabolic investigations. Electrophysiological function study is the golden standard of judging GOF of LOF variants. Seizure onset age could be considered as a preliminarily judging method, which should be verified by the whole‐cell patch‐clamp