Huntington disease (HD) is an inherited neuropsychiatric illness caused by polyglutamine expansion in the gene for the protein huntingtin (HTT)[Huntington’s Disease Collaborative Research Group, 1993]. Almost immediately upon discovery of this gene, it was recognized that the mean age of clinical onset was strongly related to length of the CAG trinucleotide expansion that codes for the polyglutamine repeat [Duyao et al., 1993; Stine et al., 1993]. Since then, numerous statistical models have been published that fit relationships between CAG length and clinical onset.

We begin by reviewing the various published models, focusing on substantive differences between these studies and potential methodological explanations for those differences. We then test the prospective validity of two models that lend themselves to such examination, focusing on a model previously reported by Langbehn et al.[2004]. We do this using data from a prospective longitudinal study of the development of HD, PREDICT-HD [Paulsen et al., 2006, 2008].