Our findings show that a variant in the X-chromosome essential splicing factor GPKOW is the likely cause of a male-lethal disorder featuring microcephaly and IUGR, and add to the growing number spliceosomal gene variants implicated in severe developmental disorders, highlighting the crucial role of pre-mRNA splicing in human development.8 Further investigations to elucidate the role of GPKOW in normal development are warranted. Here, GPKOW is linked to microcephaly.