Dystonia

INDEX

Mutations in the TOR1A gene (torsin family 1 member A) encoding TorsinA, a member of the AAA+ superfamily (ATPases associated with a variety of cellular activities), are a cause of early-onset generalized dystonia. The first and so far the only clearly established mutation is a 3-bp deletion in the TOR1A gene(c.904_906delGAG;p.302delGlu).This mutation is frequently found among Ashkenazi Jewish patients due to a founder effect. Different rare missense and in-frame mutations lack unequivocal confirmation of pathogenicity.

DYT-TOR1A dystonia usually presents as dystonia in an extremity in childhood. The symptoms later progress to other body parts but typically spare the face and neck. There is variable expressivity ranging from severe childhood-onset generalized to late-onset focal dystonia (including writer’s cramp and dystonic tremor), and about two thirds of the mutation carriers remain unaffected throughout their life (reduced penetrance). The condition is autosomal dominant.  Deep brain stimulation has repeatedly been shown to be an effective treatment option.