BPAN. The Only X-Linked Dominant NBIA Disorder

Tobias B. Haack, Penny Hogarth, Allison Gregory, Holger Prokisch, Susan J. Hayflick

Research output: Chapter in Book/Report/Conference proceedingChapter

23 Scopus citations

Abstract

Beta-propeller protein-associated neurodegeneration (BPAN) is the most recently identified subtype of neurodegeneration with brain iron accumulation (NBIA), being unique with respect to the underlying disease genetics, the associated clinical presentation, and the suggested pathomechanism. Mutations in X-chromosomal WDR45 arise de novo; however, the dominant pattern of inheritance is unusual for an X-linked disorder and additional mechanisms such as X-inactivation or somatic mosaicism are likely to contribute to the phenotype that is indistinguishable between males and females. The course of the disease is two-staged with developmental delay and intellectual disability in childhood and a second phase of rapid neurological deterioration characterized by parkinsonism and dementia occurring in adolescence or early adulthood. At this time, neuroimaging findings are characteristic and provide excellent diagnostic guidance. There is increasing evidence that human WDR45 deficiency impairs autophagy, thereby raising the possibility that this rare disorder will offer insights into more common neurodegenerative disorders such as Parkinson or Alzheimer disease.

Original languageEnglish (US)
Title of host publicationInternational Review of Neurobiology
PublisherAcademic Press Inc.
Pages85-90
Number of pages6
DOIs
StatePublished - 2013

Publication series

NameInternational Review of Neurobiology
Volume110
ISSN (Print)0074-7742

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Keywords

  • Autophagy
  • De novo mutations
  • Dyskinesia
  • Intellectual disability
  • Parkinsonism
  • Rett-like
  • WDR45
  • X-linked

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Haack, T. B., Hogarth, P., Gregory, A., Prokisch, H., & Hayflick, S. J. (2013). BPAN. The Only X-Linked Dominant NBIA Disorder. In International Review of Neurobiology (pp. 85-90). (International Review of Neurobiology; Vol. 110). Academic Press Inc.. https://doi.org/10.1016/B978-0-12-410502-7.00005-3