Figure 2.

Huntington's disease is a lifelong disorder. The schematic diagram depicts the lifelines of a typical normal individual and a typical individual carrying the HD mutation. The darkening arrows illustrate the changes that occur during the lifetime of each individual as they proceed from conception to death. The use of different colors denotes that the HD subject is never the same as the normal individual, differing even shortly after conception in the expression of mutant huntingtin and its biochemical consequences. The differences lead over time to a variety of phenotypes whose order of appearance and interdependence are not well defined, particularly prior to clinical diagnosis, which is currently based upon the characteristic movement disorder. Death ensues after an inexorable clinical decline, usually approximately 15 years after the appearance of diagnostic movements. Genetic modifiers (blue upward arrows), which could theoretically act at any stage and on any phenotype, are currently being sought for the phenotype of diagnostic motor onset, as the residual variation in this phenotype after accounting for the effect of the HD CAG repeat is highly heritable.