Currently, it is unclear why disruption of Pcdhgc4 in mice leads to neonatal lethality, whereas biallelic loss-of-function variants in human, as observed in our patients, result in a milder neurodevelopmental disorder comprising progressive microcephaly, seizures, and intellectual disability, especially when considering that both humans and mice share the same set of 22 members within the γ-PCDH cluster. This evidence concerns the gene PCDHGC4 and microcephaly.