Primary dystonia (DYT) has traditionally been attributed to basal ganglia dysfunction. Recent studies expanded this picture suggesting primary DYT as a circuit disorder. This study investigated structural neural pathways in clinically manifesting and non-manifesting individuals with several DYT genotypes using a network approach.This study included a large series of clinically manifesting and non-manifesting DYT mutation carriers. Specifically, we enrolled 9 asymptomatic mutation carriers (4 DYT1, 4 DYT6, 1 DYT10) and 26 symptomatic mutation carriers (7 DYT1, 7 DYT6, 9 DYT5 or dopa-responsive dystonia, 1 DYT18, 1 DYT10, and 1 DYT25). 37 age- and sex-matched healthy controls were also studied. Subjects underwent 3D T1 weighted and diffusion tensor (DT) MRI. The human macroscale connectome – a comprehensive map describing all neural connections between large-scale brain regions – was constructed from DT MRI. Tissue segmentation was performed on T1 images using Freesurfer. Parcellation of the segmented gray matter mask into 83 distinct brain regions was based on Desikan atlas, including basal ganglia. Tractography was performed to reconstruct the white matter tracts forming the structural brain network. From the total collection of reconstructed streamlines those connecting each couple of nodes i and j were selected. Then, from the selected fiber streamlines, the average fractional anisotropy (FA) and mean diffusivity (MD) values were computed. This value entered into cell c(i,j) in the matrix. The affected structural connections in patients with manifesting and non-manifesting DYT relative to healthy controls and each other were investigated using Network-Based Statistic (p<0.01, 10.000 permutations).Compared to controls, asymptomatic mutation carriers showed a basal ganglia/frontal subnetwork characterized by decreased FA and increased MD including the left putamen, precentral gyrus, middle and superior frontal gyri, middle temporal, and insula (Fig. 1). Clinically manifesting DYT mutation carriers relative to controls showed an altered subnetwork characterized by increased MD connecting left putamen, middle and superior frontal gyri, orbitofrontal cortex, middle temporal, insula and right anterior cingulate cortex (Fig. 2). No differences were found between symptomatic and asymptomatic DYT subjects. A trend toward a greater disconnection was observed in symptomatic DYT1 relative to DYT6 subjects.Our findings suggest that structural brain abnormalities in both clinically manifesting and non-manifesting DYT mutation carriers are distributed at a network level, beyond the basal ganglia/sensorimotor cortex regions. Studying of asymptomatic mutation carriers offered the possibility of identifying genotype-related trait characteristics without the confound of clinical symptoms providing new insights into understanding DYT generation.