Self-Limited Focal Epilepsies in Childhood: How Many and How to Treat

Self-limited focal epilepsies in childhood (SELFEs), formerly referred to as "benign epilepsies in childhood", constitute a heterogeneous group of epileptic conditions with onset predominantly in the neonatal, infantile, and childhood periods. A defining feature of these syndromes is that seizures arise without underlying structural, metabolic, or other demonstrable cerebral pathology, and the overall clinical trajectory is expected to be favorable, with seizures resolving spontaneously over time. Current nosological frameworks divide SELFEs into two broad categories according to age at onset: (a) neonatal and infantile forms, encompassing self-limited familial and non-familial neonatal, neonatal-infantile, and infantile epilepsies, genetic epilepsy with febrile seizures plus (GEFS+), and myoclonic epilepsy of infancy (MEI); and (b) childhood-onset forms, including self-limited epilepsy with centrotemporal spikes (SeLECTS), self-limited epilepsy with autonomic seizures (SeLEAS), childhood occipital visual epilepsy (COVE), and photosensitive occipital lobe epilepsy (POLE). Despite their historically "benign" label, there is no general agreement to include GEFS + and MEI among the group of SELFEs as both these conditions have been not classified as focal epilepsy in general. Accumulating evidence shows that a subset of affected children subsequently develop additional seizure types, cognitive deterioration, and behavioral or neuropsychiatric difficulties-outcomes that the word "benign" does not adequately communicate. Advances in molecular genetics have identified pathogenic variants affecting ion channels, synaptic transmission, and neuronal excitability, reshaping current understanding of disease mechanisms and phenotypic variability across these syndromes. This review highlights clinically relevant challenges in the diagnosis and management of SELFEs, critically examines emerging genotype-phenotype correlations, and provides evidence-based recommendations for antiseizure medication initiation and withdrawal tailored to individual syndrome characteristics and risk profiles.