Novel WDR45 Mutation and Pathognomonic BPAN Imaging in a Young Female With Mild Cognitive Delay

Abstract
β-propeller protein-associated neurodegeneration (BPAN) is a recently identified X-linked dominant form of neurodegeneration with brain iron accumulation caused by mutations in the WDR45 gene. BPAN commonly presents as global developmental delay in childhood with rapid onset of parkinsonism and dementia in early adulthood and associated pathognomonic changes seen on brain MRI. In this case report, we present a pediatric patient with mild cognitive delay and pathognomonic MRI changes indicative of BPAN preceding neurologic deterioration who is found to have a novel de novo mutation in the WDR45 gene.

Abbreviations:
BPAN — β-propeller protein-associated neurodegeneration
NBIA — neurodegeneration with brain iron accumulation
Neurodegeneration with brain iron accumulation (NBIA) is a genetically and clinically heterogeneous group of disorders with the common feature of iron deposition in the basal ganglia and substantia nigra. β-propeller protein-associated neurodegeneration (BPAN) is a recently identified, X-linked dominant form of NBIA characterized by 2 phases of disease: intellectual disability and global developmental delay in childhood with rapid progressive onset of parkinsonism, dystonia, and dementia in early adulthood.1 Previously referred to as static encephalopathy of childhood with neurodegeneration, BPAN involves de novo mutations in the WDR45 gene, which plays a critical role in autophagy through a WD40 repeat protein with a β-propeller platform structure.2 In this case report, we present a young woman with MRI changes preceding clinical progression who possesses a novel, heterozygous mutation in WDR45: c.251A>G (p.Asp84Gly).

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  1. Michelle Long

    Investigator, CHEO Research Institute

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