Adult-onset idiopathic dystonia: phenotype and mechanism changes “as time goes by”

Abstract

Adult-onset idiopathic dystonia is thought to be an autosomal dominant disorder with markedly reduced penetrance and heterogeneous clinical presentation. It has been known for a long time that age may affect the clinical phenomenology of the condition, at least in terms of the site of dystonia onset. The aim of this paper is to understand whether age and aging may play a role in the natural history of adult-onset idiopathic dystonia and in the mechanisms underlying its development and progression. Aging may increase abnormalities in cortical/subcortical excitability manifested by patients with different forms of adult-onset idiopathic dystonia, thus enhancing susceptibility to dystonia development, worsening spasm severity, at least in blepharospasm, and favoring perhaps the spread of dystonia to near body sites. The relationship between age of onset and site of onset in adult-onset idiopathic dystonia (AOID) might reflect age- and body-site-specific environmental risk factors that would drive the variable clinical expression of individuals carrying dystonia-susceptibility gene(s).