|Ahead of print
Characteristic neuroimaging findings in β-propeller protein-associated neurodegeneration
Center for Pediatric Neurology, Cleveland Clinic, Neurological Institute, Cleveland, OH, USA
|Date of Submission||19-Jun-2020|
|Date of Decision||27-Aug-2020|
|Date of Acceptance||01-Oct-2020|
|Date of Web Publication||12-Jul-2021|
Center for Pediatric Neurology, Cleveland Clinic, Neurological Institute, 9500 Euclid Avenue/S60, Cleveland, OH.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
β-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation. Characteristic neuroimaging features can help distinguish BPAN from other disorders and prompt confirmatory genetic testing.
Keywords: Basal ganglia, genetics, imaging, movement disorders, NBIA
A 6-year-old male presented with generalized epilepsy and severe global developmental delay noted since infancy. Expressive language was most prominently impaired. He was nonambulatory. Other notable findings included optic nerve pallor, Parkinsonism More Details, and dystonia. Magnetic resonance imaging [MRI, Figure 1]] showed bilateral hypointense signal in the substantia nigra and globus pallidus (more pronounced in the substantia nigra) on T2/FLAIR sequences. Susceptibility weighted imaging showed prominent corresponding areas of hypointensity. The “eye of the tiger” sign was not seen. Genetic testing showed a hemizygous pathogenic variant in the WDR45 gene, c.197T>A (p.V66E), consistent with β-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA).
|Figure 1: MRI shows hypointense signal in the bilateral substantia nigra on FLAIR (A) and SWI sequences (B). Hypointense signal in the bilateral globus pallidus on FLAIR (C) and SWI (D) sequences. Hypointensity most prominent in the bilateral substantia nigra compared to other regions on T2-weighted sequence (E)|
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BPAN is the only NBIA disorder inherited in an X-linked dominant fashion. The first manifestations of BPAN are typically global developmental delay and intellectual disability in early childhood. Patients typically have expressive language delays that are disproportionate to their other abilities. Epilepsy frequently develops in early childhood, with seizure burden tending to improve with age. However, cognitive decline and parkinsonism begin to dominant the clinical picture later in childhood. The decline in cognition from an already abnormal baseline and emergence of a hypokinetic movement disorder usually prompts neuroimaging. MRI typically shows T2-weighted hypointensities in the substantia nigra and globus pallidus, indicative of iron deposition. In BPAN, the substantia nigra is usually more hypointense than the globus pallidus, which is a specific finding that can help distinguish BPAN from other NBIA disorders. In the setting of MRI suggestive of BPAN, confirmatory diagnosis is made with genetic testing, which shows a pathogenic variant in the WDR45 gene.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Haack TB, Hogarth P, Gregory A, Prokisch H, Hayflick SJ. BPAN: the only X-linked dominant NBIA disorder. Int Rev Neurobiol 2013;110:85-90. doi:10.1016/B978-0-12-410502-7.00005-3
Gregory A, Kurian MA, Haack T, Hayflick SJ, Hogarth P. Beta-propeller protein-associated neurodegeneration. In: Adam MP, Ardinger HH, Pagon RA, et al
, editors. GeneReviews® [Internet]. Seattle, WA: University of Washington; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK424403/. [Last access date 2020 Aug 27].