Background Growing evidence supports the notion that abnormal brain development may be an important component of Huntington’s disease pathoetiology. To assess this, the current study was designed to evaluate brain function of the motor system in children at risk for HD.

Methods Children (6–18 years) at risk for HD are enrolled along with healthy children (HC) with no family history of HD. Participants are tested for gene-expansion for research purposes only. The sample included 46 children who were gene-expanded (GE), 50 gene non-expanded (GNE), and 120 HC. All participants underwent a brain MRI. Measures were obtained for resting state functional connectivity and levels of neurochemicals using spectroscopy. Motor performance was obtained using the Physical and Neurologic Examination of Subtle Signs (PANESS).

Results GNE and HC subjects had no significant differences in any measures, thus were combined. The GE group compared to the combined group showed abnormalities in the functional connectivity of the motor system. Seed voxels placed in the putamen were associated with significantly lower connectivity to the pre-central gyrus bilaterally. In the Spectroscopy measures, the GE group had increased N-acetyl aspartate (NAA) level and decreased Glutamate levels. All motor measures were correlated with CAG repeat length such that those children with CAG repeat length 46 and above had significantly abnormal motor scores compared to the combined group.

Conclusion GE children who were, on average 30 years from onset of disease showed significant abnormalities in the function of striatum and associated motor regions.