Cdc42 Guanine Nucleotide Exchange Factor 9 (<i>ARHGEF9</i>) gene variants have been linked to DEE, yet novel variants and their phenotypic presentations remain incompletely characterized.<h4>Clinical cases</h4>Herein, we describe two siblings with DEE caused by a novel deletion variant in the <i>ARHGEF9</i> gene. The gene discussed is ARHGEF9; the disease is developmental and epileptic encephalopathy.