Another downregulated gene, ESAM, has been recently associated with a rare neurodevelopmental phenotype characterised by DD/ID, epilepsy, absent or severely delayed speech, ventriculomegaly, thin corpus callosum, variable microcephaly and intracranial haemorrhage, which already manifest in the antenatal period in individuals with biallelic loss-of-function variants that completely abrogate gene expression [25]. The gene discussed is ESAM; the disease is microcephaly.