Characteristic MRI findings in beta-propeller protein-associated neurodegeneration (BPAN)
Yuta Ichinose1, Michiaki Miwa1, Akiko Onohara1
1Department of Neurology (YI, MM, AO, KS, YT), Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan; Department of Neurology (KO), Juntendo University School of Medicine, Tokyo, Japan; and Department of Human Genetics (HS, NM), Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Abstract:
A 31-year-old woman presented with severe dystonia-parkinsonism. She had nonprogressive psychomotor retardation and cognitive dysfunction from childhood without evidence of dystonia or parkinsonism. At age 30, she then developed severe dystonia and gait disturbance. There was neither dystonia nor parkinsonism before age 30. MRI revealed cerebral atrophy and iron accumulation in the globus pallidus and substantia nigra (figure 1, A-D). The characteristic MRI findings were hyperintensity of the substantia nigra with a central band of hypointensity in T1-weighted axial slices (figure 1, B). Beta-propeller protein-associated neurodegeneration (BPAN) was diagnosed based on MRI findings and identification of a novel heterozygous mutation in the WDR45 gene (NM_007075.3: c.519+1_519+3del) (figure 2). This is a neurodegeneration involving brain iron accumulation (NBIA) characterized by psychomotor retardation from childhood and dystonia-parkinsonism in midadulthood.1,2 Although we could not analyze the father's gene since he had died, the mother had no mutation in the WDR45 gene (figure 2). Thus, it might be a de novo mutation in the WDR45 gene, as reported previously.1,2.
Insights
Beta-propeller protein-associated neurodegeneration (BPAN) is a rare brain disorder. This case highlights a novel WDR45 gene mutation causing childhood developmental delays and adult-onset dystonia-parkinsonism.
Area of Science:
- Neuroscience
- Genetics
- Radiology
Background:
- Beta-propeller protein-associated neurodegeneration (BPAN) is a rare neurodegenerative disorder.
- It is characterized by early-onset psychomotor retardation and later-onset dystonia-parkinsonism.
- BPAN falls under the umbrella of neurodegeneration with brain iron accumulation (NBIA).
Observation:
- A 31-year-old woman presented with severe dystonia-parkinsonism and gait disturbance, developing in her third decade.
- Childhood history revealed nonprogressive psychomotor retardation and cognitive dysfunction.
- Brain MRI showed cerebral atrophy and characteristic iron accumulation in the globus pallidus and substantia nigra, including a specific T1-weighted hyperintensity pattern in the substantia nigra.
Findings:
- Diagnosis of BPAN was confirmed by characteristic MRI findings and the identification of a novel heterozygous mutation (c.519+1_519+3del) in the WDR45 gene.
- The mutation was identified as potentially de novo, as the mother did not carry the mutation.
Implications:
- This case expands the understanding of WDR45 mutations and their phenotypic spectrum in BPAN.
- Highlights the importance of genetic testing in conjunction with neuroimaging for diagnosing NBIA disorders.
- Contributes to the genetic landscape of neurodegenerative diseases with brain iron accumulation.
Related Concept Videos
01:37Neural Regulation
01:24Parkinson Disease ll: Pathophysiology