DRPLA (dentatorubral-pallidoluysian atrophy) is a progressive neurologic disorder characterized by ataxia, cognitive decline, myoclonus, chorea, epilepsy, and psychiatric manifestations.
Overview
- Hallmark features
- Ataxia
- Cognitive decline
- Myoclonus
- Chorea
- Epilepsy and psychiatric manifestations
Clinical Features
- Naito-Oyanagi disease
- Haw River syndrome
- ATN1-related dentatorubral-pallidoluysian atrophy
- Age of onset: 0-72 years (mean: 31.5 years)
- Inversely related to CAG repeat size in the ATN1 gene
- Disease duration: ~8 years (range: 0-35 years)
- Mean age at death: 49 years (range: 18-80 years)
Additional Clinical Manifestations
- Juvenile Onset (before age 20 years):
- Associated with ≥65 CAG repeats
- Key features:
- Developmental delay and progressive intellectual disability
- Myoclonus and epilepsy (progressive myoclonic epilepsy phenotype)
- Developmental regression, ADHD, autism spectrum disorder, microcephaly (variable findings)
Family History
- Resistant to anti-seizure medications
- Types evolve over time:
- Early: Partial and brief generalized seizures (atypical absence, myoclonic)
- Later: Generalized tonic-clonic seizures
Note: Absence of a known family history does not rule out diagnosis.
Molecular Genetics
- Associated with <65 CAG repeats
- Mean age of onset: 48 years
- Prominent features:
- Ataxia, choreoathetosis
- Personality changes (e.g., delusions, hallucinations, aggression)
- Cognitive decline affecting attention, executive function, visuoconstruction; memory relatively preserved
- Seizures (in younger adults)
- Isolated ataxia in older adults (age >60 years)
- REM sleep behavior disorder (RBD), insomnia, circadian rhythm disruption
Genotype-Phenotype Correlations in DRPLA
- All ages:
- Dysphagia (late stages)
- Choreoathetosis, dystonia, myoclonus, oculomotor impairments
- Postural instability, optic atrophy, corneal endothelial degeneration
Neuroimaging