Developmental epilepsy-dyskinetic encephalopathy (DEDE) is a collective term for a group of genetic disorders characterized by refractory involuntary (hyperkinetic) movements, often accompanied by severe drug-resistant epilepsy and developmental delay or regression, with a high rate of genetic diagnosis. Driven by multidisciplinary technologies—particularly next-generation sequencing—epilepsy genetics has made significant strides. This review delineates the landscape of genetic etiologies, clinical presentations and advancements in precision medicine for developmental epilepsy-dyskinetic encephalopathy. The manuscript focuses on how specific pathogenic genes disrupt core neurobiological processes, including ion channel function and neurotransmitter metabolism. It summarizes personalized treatment approaches already applied to certain monogenic epilepsies, heralding the era of precision medicine.
Epilepsy is a highly prevalent neurological disorder worldwide. With the widespread application of genetic testing, the critical role of genetic factors in epilepsy has been increasingly recognized. Mutations in voltage-gated sodium channels constitute the primary etiology of hereditary epilepsy. Composed of α and β subunits, these channels exhibit prominent cell-type specificity and developmental temporal dependence in their distribution across the central nervous system. Sodium channel mutations exert bidirectional pathogenic effects, namely loss of function (LOF) and gain of function (GOF). LOF mutations induce network disinhibition by impairing the function of GABAergic inhibitory interneurons, whereas GOF mutations directly amplify the firing of excitatory pyramidal neurons and trigger hyperexcitability. The combined effects of LOF and GOF determine epileptic phenotypes and drug responsiveness. This paper systematically reviews the structure, genetic characteristics and bidirectional pathogenic mechanisms of sodium channels, the phenotypic spectrum of key subtypes (SCN1A, SCN2A, SCN3A, SCN8A, SCN1B), research models, as well as precision therapeutic strategies. It provides up-to-date research advances for mechanistic investigation and individualized precision clinical diagnosis and treatment of hereditary epilepsy.