Beta-propeller Protein-Associated Neurodegeneration (BPAN) is caused by mutations in the gene WDR45, located on the X chromosome. Most affected individuals identified so far have been simplex cases, meaning they are the only person in their family to have the disease. The majority are females, indicating the mutations are new, or de novo, and suggesting that mutations may be lethal in most males before birth. There are rare instances of recurrence in a sibling. In these cases, the mutation was inherited from a midly affected parent. 

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Clinical Diagnosis

An MRI of the brain showing evidence of increased iron in the substantia nigra and globus pallidus is an indication of BPAN, along with the following clinical history:

Affected individuals are developmentally delayed during childhood with slow motor and cognitive gains. Most children are described as clumsy with an ataxic gait unsteady, staggering movements while walking. Generally, the individuals are healthy, but they may exhibit other problems. Seizures are common, as are sleep disorders.

Often there is a loss of brain cells and tissue in the cerebral area of the brain, a condition called generalized cerebral atrophy. During adolescence or adulthood, affected individuals experience a relatively sudden onset of progressive dystonia-parkinsonism and cognitive decline.

One possibly unique feature of BPAN can be detected on an MRI of the brain: the presence of a bright halo seen in a certain view (T-1 weighted) in the substantia nigra and cerebral peduncles. Hyperintense signal (an abnormality that shows as bright white on MRI) in this region seems to appear at the same time or soon after the clinical symptoms of progressive dystonia-parkinsonism appear. On an MRI T-2 weighted view there is a hypointense signal (an abnormality that appears dark on the MRI) in the substantia nigra that is usually detectable by early in the second decade of life and possibly sooner. This feature would justify genetic testing for mutations in WDR45.

L-DOPA, a drug commonly used to treat Parkinson’s disease, provides substantial initial benefit to BPAN patients, but the benefit is short-lived, as it causes dyskinesias, a difficulty or distortion in performing voluntary movements and the presence of involuntary movements.


With genetic testing available, the diagnosis of BPAN during childhood is now possible. Earlier detection will not only provide families with a diagnosis and accurate assessment of recurrence risk, but may enable earlier intervention for subtle symptoms of parkinsonism.


In early 2012, Dr. Tobias Haack of Helmholtz Zentrum München, a German research institution, received a $40,000 grant from the NBIA Disorders Association for his study: “Next generation sequencing for disease gene identification and genetic testing in NBIA.” The collaborative project involving the lab of Dr. Susan Hayflick at the Oregon Health & Science University, applied next generation sequencing to individuals suffering from NBIA with no known genetic cause. This study resulted in the finding of the WDR45 gene, causing BPAN, with the findings reported in December 2012 in the American Journal of Human Genetics.


Please see GeneReviews and the links to the research papers in the right column on this page if you wish to read about the gene discovery and information on BPAN in more depth. Also check out the latest research articles published at our scientific publications link under Research. 




BPAN Consensus Guidelines

Guidelines providing best practices for BPAN now available to clinicians


BPAN mouse model now available to researchers


GeneReviews® - BPAN

Beta-Propeller Protein-Associated Neurodegeneration

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More Information: BPAN

BPAN: The Only X-Linked Dominant NBIA Disorder
Read Article

Beta-Propeller Protein-Associated Neurodegeneration: A new X-linked dominant disorder with brain iron accumulation
Read Abstract

Exome Sequencing Reveals De Novo WDR45 Mutations Causing a Phenotypically Distinct, X-Linked Dominant Form of NBIA
Read Report

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