Neurodevelopmental Disorder and Late‐Onset Degenerative Parkinsonism in a Patient with a WDR45 Defect

Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked dominant disorder due to a WDR45 defect that presents with the same phenotype in males and females [1]. WDR45 encodes for the WD40 repeat protein, which is involved in the biogenesis and maturation of autophagosomes due to its interaction with phosphoinositide 4 (WIPI4). Clinical presentation of WDR45 defects is characterized by early-onset global developmental delay, epilepsy, and ataxia and evolves to severe intellectual disability and cognitive deterioration, dystonia, and parkinsonism after the second decade of life. Brain MRI diagnostic markers include iron deposition in the substantia nigra and globus pallidus and cerebral atrophy. We report the clinical history of a female patient with a de novo WDR45 variant who presented with Angelman-like syndrome during childhood, years before the emergence of degenerative parkinsonism.