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The combination of congenital bilateral perisylvian syndrome (CBPS) with lower motor neuron dysfunction remains unusual and suggests a potential common genetic insult affecting basic neurodevelopmental processes. Here we identify a putatively pathogenic missense mutation in the  MCF2  gene in a boy with CBPS .  Using in utero electroporation to genetically manipulate cortical neurons during corticogenesis, we demonstrate that the mouse  Mcf2  gene controls the embryonic migration of cortical projection neurons. Strikingly, we find that the CBPS‐associated  MCF2  mutation impairs cortical laminar positioning, supporting the hypothesis that alterations in the process of embryonic neuronal migration can lead to rare cases of CBPS.

MCF2 is linked to a complex perisylvian syndrome and affects cortical lamination