The discovery of a causative gene mutation (abnormal expansion of the CAG repeat in DRPLA gene) triggered the development of novel neuropathology in DRPLA, which has suggested that Selleck CB-839 polyglutamine-related pathogenesis involves a wide range of central nervous system regions far beyond the systems previously reported to be affected. It is now likely that DRPLA has an aspect of neuronal storage disorder and has multiple system

degeneration, the lesion distribution of which varies depending on the CAG repeat sizes in the causative gene. Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder and is now also known as one of the CAG repeat (polyglutamine) diseases. According to a review article of DRPLA by Kanazawa,1 the first case of hereditary DRPLA was reported by Titica and Bogaert in 1946,2 who described two patients in a single family. Their clinical features included progressive hemiballism with choreoathetosis cerebellar ataxia and dementia. Neuropathology of the one case disclosed a combined degeneration of the pallidoluysian and dentatorubral systems. In 1958, Smith et al. reported a sporadic case of DRPLA without a family history, who showed cerebellar ataxia with combined degeneration of the dentato-rubral and pallido-Luysian CAL-101 concentration systems.3 The study which

laid special emphasis on the heritability of DRPLA was started by Naito et al. in 1972.4 The authors reported two families suffering from progressive myoclonus epilepsy (PME) with autosomal dominant transmission. In 1976, Oyanagi et al. reported autopsy findings of eight patients with degenerative PME, and confirmed the combined

degeneration of the two systems as the pathology responsible for PME and other neurological symptoms.5 It is interesting that the two sporadic patients in the study were later reclassified as myoclonus epilepsy with ragged-red fiber and essential myoclonus Urocanase and epilepsy. In 1982, Naito and Oyanagi proposed the name “hereditary dentatorubral-pallidoluysian atrophy” for the disease conditions characterized by the following features: (i) myoclonus epilepsy syndrome with or without cerebellar ataxia or choreoathetosis or both; (ii) dentatorubral-pallidoluysian atrophy; and (iii) autosomal dominant heredity.6 Dentatorubral-pallidoluysian atrophy patients show various symptoms, such as myoclonus, epilepsy, ataxia, choreoathetosis and dementia, and the combinations of these symptoms are determined by the age at onset.7 Patients with earlier onset (generally below the age of 20 years) show progressive myoclonus, epilepsy and mental retardation (juvenile type). Epileptic seizures are a feature in all patients with onset before the age of 20, and the frequency of seizures decreases with age after 20.