Here, we discuss recent updates on WIPI4's mechanistic role in autophagy and link the neuropathological manifestations of BPAN's biphasic infantile onset (epilepsy, autism) and adolescent onset (dystonic, Parkinsonism, dementia) phenotypes to neurological consequences of autophagy impairment that are now known or emerging in many other neurodevelopmental and neurodegenerative disorders.
Mutations in the WDR45 gene have been identified as causative for the only X-linked type of neurodegeneration with brain iron accumulation (NBIA), clinically characterized by global developmental delay in childhood, followed by a secondary neurological decline with parkinsonism and/or dementia in adolescence or early adulthood.