We prospectively evaluated 129 patients with manifest Huntington's disease (HD) to determine the rate of illness progression and the clinical features that correlate with functional decline. A single examiner evaluated each patient using the HD Functional Capacity Scale. Standardized motor performance was also assessed in 94 of the patients (73%) using the HD Rating Scale. Total Functional Capacity declined at a rate of 0.63 +/- 0.75 U per year. As functional capacity worsened, chorea lessened, and dystonia intensified. There was no correlation between rate of functional decline and age at onset of HD, body weight, gender of affected parent, or history of neuroleptic use.

The genetic defect causing Huntington's disease (HD) has been identified as an unstable expansion of a trinucleotide (CAG) repeat sequence within the coding region of the IT15 gene on chromosome 4. In 50 patients with manifest HD who were evaluated prospectively and uniformly, we examined the relationship between the extent of the DNA expansion and the rate of illness progression. Although the length of CAG repeats showed a strong inverse correlation with the age at onset of HD, there was no such relationship between the number of CAG repeats and the rate of clinical decline. These findings suggest that the CAG repeat length may influence or trigger the onset of HD, but other genetic, neurobiological, or environmental factors contribute to the progression of illness and the underlying pace ofneuronal degeneration.