Research focused on identifying effective interventions for individuals with Down syndrome is increasingly informed by the behavioral phenotype -- a profile of performance associated with a genetic abnormality. Recent studies substantiate the efficacy of phenotypically aligned instruction in improving basic reading skills for children with Down syndrome. However, research does not yet relate the reading intervention with improvements in curriculum-based measures, including the reading of connected text. The aim of this study was to examine the effect of phenotypically aligned reading instruction on the acquisition of advanced graphemes (e.g., digraphs) for children with Down syndrome. Four children received reading instruction in their typical education environment. Although findings from proximal measures provide support for the intervention, performance on curriculum-based measures was mixed. Future research should continue to probe the impact of the intervention on a diverse range of skills.