Growth and Development of the Striatum in Huntington's Disease

Huntington's Disease (HD) is an autosomal dominant disease manifested in a triad of
cognitive, psychiatric, and motor signs and symptoms. HD is caused by a triplet repeat
(CAG)expansion in the gene Huntingtin (HTT). This disease has classically been conceptualized
as a neurodegenerative disease. However, recent evidence suggests that abnormal brain
development may play an important role in the etiology of HD. Huntingtin (HTT)is expressed
during development and through life. In animal studies, the HTT gene has been shown to be
vital for brain development. This suggests that a mutant form of HTT (gene-expanded or CAG
repeats of 40 and above) would affect normal brain development. In addition, studies in
adults who are gene-expanded for HD, but have not yet manifested the illness, (pre-HD
subjects) have significant changes in the structure of their brain, even up to 20 years
before onset of clinical diagnosis. How far back these changes are evident is unknown. One
possibility is that these brain changes are present throughout life, due to changes in brain
development,though initially associated with only subtle functional abnormalities.

In an effort to better understand the developmental aspects of this brain disease, the
current study proposes to evaluate brain structure and function in children, adolescents, and
young adults (ages 6-25) who are at risk for developing HD - those who have a parent or
grandparent with HD. Brain structure will be evaluating using Magnetic Resonance Imaging
(MRI) with quantitative measures of the entire brain, cerebral cortex, as well as white
matter integrity via Diffusion Tensor Imaging. Brain function will be assessed by cognitive
tests, physical and neurologic evaluation, behavioral assessment, and quantitative
craniofacial structure assessment. Subjects that are gene-expanded (GE) will be compared to
subjects who are gene non-expanded (GNE) and as well to matched healthy controls. Changes in
brain structure and/or function in the GE group, compared to both GNE and control groups,
would lend support to the notion that this disease has an important developmental component.