dentatorubral-pallidoluysian atrophy (DRPLA)

Epidemiology

• relative common in Japan
• Haw River syndrome is variant described in African-Americans in North Carolina

Pathology

• loss of neurons & gliosis in the dentate nucleus, subthalamic nucleus, globus pallidus
• neuronal intranuclear inclusions
  • striatum, pontine nuclei, inferior olive, cerebellar cortex dentate nucleus
  • incidence is low, roughly 1-3% of neurons
• reaction of transglutaminases & caspases implicated in neurotoxicity

Genetics

• autosomal dominant
• trinucleotide repeat expansion (CAG) in gene for atrophin-1 (ATN1), normally varies from 7 to 23 CAG copies, expansion to ~49 to 75+ in DRPLA gene
• longer expansions result in earlier onset & more severe clinical manifestations

Clinical manifestations

• cerebellar ataxia
• rigidity
• choreoathetosis
• myoclonic epilepsy
• dementia
• hyperreflexia
• slow saccades
• onset of symptoms usually occurs in the 2nd decade of life
• death usually occurs in the 4th decade of life

Laboratory

• ATN1 gene CAG repeats

Diagnostic procedures

• EEG

Radiology

• magnetic resonance imaging (MRI)
  • atrophy of cerebellum, brainstem
  • calcification of basal ganglia
  • leukodystrophy

More general terms

• polyglutamine expansion disorder

Additional terms

• atrophin-1; dentatorubral-pallidoluysian atrophy protein (ATN1, D12S755E, DRPLA)
• dentatorubral-pallidoluysian atrophy gene (DRPLA gene, atrophin-1 gene)

Patient information

dentatorubral pallidoluysian atrophy patient information

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?
• OMIM: https://mirror.omim.org/entry/125370