BPAN

Beta-propeller Protein-Associated Neurodegeneration (BPAN) is caused by mutations in the gene WDR45, located on the X chromosome.

 

To date, all 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 are lethal in most males before birth.

Clinical Diagnosis of BPAN

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:

  • 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. 

  • 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.

  • 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.

Please visit the NBIA Disorders Association website, which was used as a primary source for the above information.