Epileptic encephalopathies in infancy are defined as conditions where the sustained epileptic activity itself may contribute to the severe neurological and cognitive impairment. These epileptic encephalopathies include Ohtahara syndrome, early myoclonic epileptic encephalopathy, West syndrome, Dravet syndrome, and malignant migrating epilepsy in infancy. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects.
To present and discuss current knowledge regarding genetic findings in epileptic encephalopathies in infancy, phenotype-genotype correlations in different forms of paediatric epileptic encephalopathies, and the impact of these new findings in clinical practice.
Patients with unclear etiologies after performing a brain magnetic resonance imaging should be considered for a further workup, which should include an evaluation for genetic defects. Nowadays, more than 50 genes have been associated with epileptic encephalopathies in infancy. Targeted next-generation sequencing panels show a high diagnostic yield in patients with epileptic encephalopathies.
Genetic knowledge about epileptic encephalopathies in infancy has revolutionized the diagnostic approach to these disorders, and an increasing number of gene mutations have been related to their pathogenesis. A more detailed classification of epileptic encephalopathies genotypes will improve the accuracy of genotype-phenotype correlation and genetic counseling. All these developments could yield therapeutic applications such as gene therapy or antiepileptic drugs ‘tailored’ to the specific genetic markers or targets.