Rho Related BTB Domain Containing 2 (RHOBTB2) pathogenic variants cause a DE/EE with a mean age of onset of 5 months, frequent status epilepticus, hypotonia, possible microcephaly, moderate-to-profound ID, possible regression or stagnation and episodes of acute encephalopathy with hemiplegia acutely accompanied by cerebral swelling followed by atrophy. Here, RHOBTB2 is linked to microcephaly.