The multiple PDZ domain crumbs cell polarity complex component gene (MPDZ; MIM: 603785), is highly expressed in the brain across the whole lifespan. It encodes the multiple PDZ domain protein, which is a member of the NMDAR signaling complex that may play a role in the control of AMPAR potentiation and synaptic plasticity in excitatory synapses.1 Previously, MPDZ variants have been demonstrated to be associated with autosomal recessive congenital hydrocephalus-2 (HYC2; MIM: 615219) which is commonly complicated by brain abnormalities and developmental delay. Seizures were reported in only one case. The association between MPDZ and epilepsy requires clarification.