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Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation.

Inger Marie SkogseidOddveig RøsbyAne KonglundJames P ConnellyBård NedregaardGreg Eigner JablonskiNadja KvernmoAsbjørg Stray-PedersenJoel C Glover
Published in: Journal of neurodevelopmental disorders (2018)
In this patient with dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity, unprecedented brain imaging findings strongly indicate striatal neuronal/dopaminergic dysfunction as the underlying cause of the dystonia. Pallidal stimulation provided a substantial improvement of the severe generalized dystonia, which is largely sustained at 4-year follow-up, and we advise this treatment to be considered in such patients. We hypothesize that the pleiotropic manifestations of the dystonia-deafness syndrome caused by this mutation derive from diverse developmental functions of beta-actin in neural crest migration and proliferation (facial dysmorphogenesis), hair cell stereocilia function (infant-onset deafness), and altered synaptic activity patterns associated with pubertal changes in striatal function (adolescent-onset dystonia). The temporal differences in developmental onset are likely due to varying degrees of susceptibility and of compensatory upregulation of other actin variants in the affected structures.
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