Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe 
epilepsies characterized by early-onset, refractory seizures occurring in the 
context of developmental regression or plateauing. Early infantile epileptic 
encephalopathy (EIEE) is one of the earliest forms of DEE, manifesting as 
frequent epileptic spasms and characteristic electroencephalogram findings in 
early infancy. In recent years, next-generation sequencing approaches have 
identified a number of monogenic determinants underlying DEE. In the case of 
EIEE, 85 genes have been registered in Online Mendelian Inheritance in Man as 
causative genes. Model organisms are indispensable tools for understanding the 
in vivo roles of the newly identified causative genes. In this review, we first 
present an overview of epilepsy and its genetic etiology, especially focusing on 
EIEE and then briefly summarize epilepsy research using animal and 
patient-derived induced pluripotent stem cell (iPSC) models. The Drosophila 
model, which is characterized by easy gene manipulation, a short generation 
time, low cost and fewer ethical restrictions when designing experiments, is 
optimal for understanding the genetics of DEE. We therefore highlight studies 
with Drosophila models for EIEE and discuss the future development of their 
practical use.