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Characteristic neuroimaging findings in β-propeller protein-associated neurodegeneration

 Center for Pediatric Neurology, Cleveland Clinic, Neurological Institute, Cleveland, OH, USA

Date of Submission19-Jun-2020
Date of Decision27-Aug-2020
Date of Acceptance01-Oct-2020
Date of Web Publication12-Jul-2021

Correspondence Address:
Travis Larsh,
Center for Pediatric Neurology, Cleveland Clinic, Neurological Institute, 9500 Euclid Avenue/S60, Cleveland, OH.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_161_20



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

How to cite this URL:
Larsh T. Characteristic neuroimaging findings in β-propeller protein-associated neurodegeneration. J Pediatr Neurosci [Epub ahead of print] [cited 2022 Jan 22]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=321155

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.[1] Epilepsy frequently develops in early childhood, with seizure burden tending to improve with age.[2] 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.[2] 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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   References Top

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  Back to cited text no. 1
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].  Back to cited text no. 2


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