September 2025

NEUROSCIENCES

CASE REPORT: ATYPICAL PRESENTATION OF ADULT-ONSET BPAN MIMICS EARLY-ONSET PARKINSON'S DISEASE

A 48-year-old female with a WDR45 pathogenic variant and a history of mild intellectual disability since childhood presented to Northwestern Medicine with six months of left arm dexterity loss and progressive gait unsteadiness. Her symptoms responded well to levodopa; however, she developed motor fluctuations and dyskinesias after three years of treatment.

Examination Findings
  • Asymmetric parkinsonism including hypomimia, left-sided bradykinesia and rigidity, and narrow-based gait with reduced arm swing
  • No significant cognitive decline observed; continued independent functioning in daily activities

Genetic and Imaging Analysis
  • Identified a pathogenic heterozygous STOP-gain variant in WDR45
  • MRI showed features typical of beta-propeller protein-associated neurodegeneration (BPAN)
  • I-Ioflupane single photon emission computed tomography indicated decreased radiotracer uptake in the right putamen

​Conclusion
Genetic analysis confirmed the WDR45 variant, and brain imaging revealed typical BPAN characteristics. This case deviates from the usual BPAN presentation, highlighting the possibility of isolated parkinsonism in patients with WDR45 mutations. 
​
Given the rarity of WDR45 variants in early onset parkinsonism, the findings suggest that genetic testing for WDR45 may be valuable for early onset Parkinson’s disease (EOPD) cases, especially those with mild cognitive impairments.
Niccolo Mencacci, MD, PhD, Assistant Professor of Neurology at Northwestern Medicine
​Dimitri Krainc, MD, PhD, the Aaron Montgomery Ward Professor, Chair of the Department of Neurology and Director of the Simpson Querrey Center for Neurogenetics at Northwestern Medicine
Ignacio J Keller Sarmiento, MD, Instructor of Neurology at Northwestern Medicine
Mariana Hernandez Gonzalez-Monje, MD, Instructor of Neurology at Northwestern Medicine

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