Dystonia

INDEX

Mutations in the ATP1A3 gene (ATPase Na + /K + transporting subunitalpha3), encoding an ionic pump, are a cause of rapid-onset dystonia-parkinsonism (RDP). These usually present in adolescence or young adulthood. The acute onset is usually associated with a trigger such as fever, physical exertion, or emotional stress. Dystonic symptoms frequently show a rostro-caudal gradient with prominent involvement of the bulbar region with cranial/laryngeal dystonia, and are often accompanied by bradykinesia as a parkinsonian feature. Symptoms usually only respond slightly to levodopa but also to benzodiazepines.

RDP is inherited in an autosomal dominant manner with reduced penetrance. In addition, mutations in ATP1A3 have also been linked to a variety of clinical syndromes (pleiotropy) including epileptic or hemiplegic attacks, ataxia, cognitive decline, and other neurological disorders, often with a more severe course and an earlier age at onset.