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dentatorubral-pallidoluysian atrophy (DRPLA)
Epidemiology:
1) relative common in Japan
2) 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
a) striatum, pontine nuclei, inferior olive, cerebellar cortex dentate nucleus
b) 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:
1) cerebellar ataxia
2) rigidity
3) choreoathetosis
4) myoclonic epilepsy
5) dementia
6) hyperreflexia
7) slow saccades
8) onset of symptoms usually occurs in the 2nd decade of life
9) death usually occurs in the 4th decade of life
Laboratory:
- ATN1 gene CAG repeats
Special laboratory:
- EEG
Radiology:
- magnetic resonance imaging (MRI)
a) atrophy of cerebellum, brainstem
b) calcification of basal ganglia
c) leukodystrophy
Related
atrophin-1; dentatorubral-pallidoluysian atrophy protein (ATN1, D12S755E, DRPLA)
dentatorubral-pallidoluysian atrophy gene (DRPLA gene, atrophin-1 gene)
General
polyglutamine expansion disorder
Database Correlations
OMIM 125370
Kegg hsa/hsa05050
References
- Genetics Home Reference: Dentatorubral-pallidoluysian atrophy
https://ghr.nlm.nih.gov/condition/dentatorubral-pallidoluysian-atrophy
- Wikipedia: Dentatorubral-pallidoluysian atrophy
https://en.wikipedia.org/wiki/Dentatorubral%E2%80%93pallidoluysian_atrophy