Here we present clinical and genetic data from five unrelated families, alongside molecular and neurobiological findings in mice that define biallelic loss-of-function variants in SLC4A10 as a cause of a severe neurodevelopmental disorder, frequently associated with microcephaly (<−3 SDS) and morphologically abnormal collapsed (slit) lateral ventricles. The gene discussed is SLC4A10; the disease is microcephaly.