Molecular diagnosis of SMC1A-related DEE relies primarily on NGS strategies, including targeted epilepsy/CdLS gene panels and trio whole-exome or whole-genome sequencing, which have markedly increased detection of de novo SMC1A loss-of-function variants in females presenting with early-onset, drug-resistant seizures and severe neurodevelopmental impairment [10,65]. This evidence concerns the gene SMC1A and developmental and epileptic encephalopathy.