Background: A heterozygous mutation in the TOR1A gene (DYT1) accounts for isolated dystonia typically presenting during childhood or adolescence, with initial involvement of one limb, spreading rapidly to other limbs and the trunk, sparing craniocervical muscles. However, atypical phenotypes, regarding age at onset, site of presentation, and spreading have been reported.
Methods and findings: In 2006, we described a large Italian family showing atypical phenotypes and intrafamilial clinical variability of DYT1-dystonia. The current article reports on a 12-year follow-up of this family, focusing on disease onset in three previously asymptomatic DYT1 mutation carriers, and the reassessment of initially affected individuals.
Conclusions: The new cases confirm the intrafamilial phenotypic heterogeneity of DYT1-dystonia. Moreover, this case series highlights that symptoms in atypical phenotypes seem not to spread significantly and in the long term, rarely worsen. Prolonged follow-up of DYT1-positive pedigrees may expand the clinical spectrum of DYT1-dystonia.
Keywords: DYT1; atypical phenotypes; dystonia; dystonic tremor; intrafamilial variability.