Objective: To expand the clinical spectrum of WDR45 deficiency.

Background: Beta-propeller protein-associated neurodegeneration (BPAN) due to WDR45 defect is a rare X-linked dominant disorder of autophagy. The clinical presentation is characterized by a biphasic course: developmental delay in early childhood and parkinsonism in young adulthood.

Method: We present the case of a 36-year-old girl with and a severe intellectual disability.
The patients presented at 30 months with an early onset generalized epilepsy, developmental delay, and a severe oral dyspraxia suggesting an Angelman-like syndrome. At the age of 6 years, speech impairment, subtle ataxia, behavioral disorders with happy dispositions, and sleep disturbance became evident. Brain TC showed brain atrophy and high-density foci in .  Under valproic acid treatment she remained seizure free.  At the age of 13 brain MRI confirmed a remarkable brain atrophy and disclosed bilateral of and substantia nigra suggesting iron accumulation.  During the second decade of life she developed a progressive , dementia and disorder with loss of adaptive skills (Vineland Adaptive Behavior Scales II edition: Composite Score= 26). Menarche occurred at the age of 20 years by progesterone stimulation. the last examination, she presented , prominent dystonic posturing of legs and generalized , action, and rest tremor, limb rigidity. She showed severe instability and can walk with support. Brain MRI at age of 35 showed a further worsening of cerebral atrophy and stable iron accumulation.

Results: An extensive metabolic work-up was unremarkable. Array CGH, and molecular analysis of Prader Willi Syndrome/Angelman Syndrome locus revealed no alteration.  Finally, NBIA panel identified a so far unreported de novo missense variant in WDR45 gene (c.439+5G>A).

Conclusion: Our findings expand the number of allelic variants associated with WDR45 deficiency. This condition should be considered in young patients presenting with Rett-like as well as Angelman-like syndrome, considering that at onset it may mimic a neurodevelopmental disorder while being a neurodegenerative disorder.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neurodevelopmental-disorder-and-parkinsonism-in-a-patient-with-wdr45-variant-a-long-term-outcome/