Dentatorubral pallidoluysian atrophy

Dentatorubral-pallidoluysian atrophy (DRPLA), also known as Haw River syndrome or Naito-Oyanagi disease, is a rare progressive neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats in the ATN1 (atrophin-1) gene on chromosome 12p13.31. Normal individuals carry 6–35 CAG repeats, while affected individuals have 48 or more repeats. The disease primarily affects the central nervous system, with neuronal degeneration occurring in the dentate nucleus of the cerebellum, the red nucleus, the globus pallidus, and the subthalamic (Luysian) nucleus. DRPLA exhibits genetic anticipation, meaning successive generations tend to develop symptoms earlier and with greater severity, particularly when the expanded allele is inherited from the father. The clinical presentation of DRPLA varies significantly depending on the age of onset. In juvenile-onset cases (before age 20), the disease typically presents with progressive myoclonus epilepsy, intellectual disability, and ataxia. In adult-onset cases (after age 20), the predominant features include cerebellar ataxia, choreoathetosis (involuntary writhing movements), and dementia. Other common symptoms include psychiatric disturbances, seizures, and progressive deterioration of motor and cognitive function. Brain MRI often reveals cerebellar and brainstem atrophy, as well as white matter changes. There is currently no cure or disease-modifying treatment for DRPLA. Management is supportive and symptomatic, focusing on controlling seizures with antiepileptic medications, managing movement disorders, and providing rehabilitation services. Psychiatric symptoms may be addressed with appropriate psychotropic medications. The disease is progressive, and prognosis varies depending on the age of onset and the number of CAG repeats. DRPLA is most prevalent in Japan, where it accounts for a significant proportion of autosomal dominant cerebellar ataxias, though cases have been reported worldwide.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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