The relationship between changes in gene expression and physical characteristics associated with Down syndrome is not well understood. Chromosome 21 genes interact with nonchromosome 21 genes to produce Down syndrome characteristics. This indirect influence, however, is difficult to empirically define due to the number, size, and complexity of the involved gene regulatory networks. This work links chromosome 21 genes to non-chromosome 21 genes known to interact in a Down syndrome phenotype through a reachability analysis of labeled transition graphs extracted from published gene regulatory network databases. The analysis provides new relations in a recently discovered link between a specific gene and Down syndrome phenotype. This type of formal analysis helps scientists direct empirical studies to unravel chromosome 21 gene interactions with the hope for therapeutic intervention.