Objective: To report clinical features of the first Austrian family with Dentatorubral-Pallidoluysian Atrophy (DRPLA).

Background: DRPLA is a progressive disorder with an autosomal-dominant mode of inheritance. Symptoms vary depending on age at onset and may include myoclonus, epilepsy, chorea, dementia and ataxia. It is caused by a CAG trinucleotide repeat expansion in the ATN1 gene on chromosome 12. Pathophysiology is thought to be mediated by intranuclear inclusion, astrocytosis and neuronal loss in the pallidoluysian and dentatorubral systems. Prevalence is highest in Japan and other Asian populations, whereas it is rare in Europe.

Method: In this family three affected members, of whom one is still alive, could be identified. This patient has been followed up at the neurological department, Medical University Innsbruck, for over 2 years on a routine basis. Clinical assessments consisted of repeated neurological examinations including ataxia rating scales. Extensive diagnostic work up was performed, including Video-EEG monitoring, cerebral MRI, neuropsychological testing and neurophysiological investigations.

Results: The 36-year-old female index patient is of Caucasian race. Disease onset was at the age of 23 with impairment of fine motor skills. She subsequently developed epileptic seizures, mainly focal complex. Ten years after disease onset she reported progressive unsteadiness with falls and cognitive decline. Clinically she showed a cerebellar syndrome and lower limb spasticity. The scale for the assessment and rating of ataxia (SARA) score progressed from 14 to 21/40 points within 2 years. Cerebral imaging showed prominent atrophy of the cerebellum and mesencephalon. Supratentorial cortical and subcortical atrophy as well as white matter abnormalities were visible. EEG exhibited diffuse cerebral dysfunction without evidence of epileptic discharges. Neuropsychological evaluation showed marked deficits in memory and executive functions. Genetic testing revealed a 63 CAG repeat expansion in the ATN1 gene.

Conclusion: To the best of our knowledge, this is the first reported family with DRPLA in Austria, clinically characterized by a progressive spinocerebellar syndrome in combination with epilepsy and cognitive impairment. Given this clinical presentation and  asuspected dominant mode of inheritance, DRPLA, although rare, should also be considered in non-Asian populations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dentatorubral-pallidoluysian-atrophy-outside-of-asia-a-case-report-of-the-first-austrian-family-harbouring-this-rare-mutation/