With growing awareness of problems with replicability and reproducibility within the field of genetic syndrome research, we outline why and how, as a field, we can collectively reform our practice with the goal of research improvement. We advocate that our research is of most impact when researchers investigate how developmental pathways and phenotypic profiles unfold. However, this neuroconstructivist approach and more traditional approaches bring many challenges, not least the problem of statistical power. Here, we outline the challenges to research in our field, and suggest solutions. In recognition that solutions can require substantial resource, we have also included less resource-intensive solutions where possible. The challenges and solutions discussed include sample size, individual differences, cross-disorder comparisons, multi-disciplinary expertise, measurement sensitivity and longitudinal data. Key recommendations include transparency and collaboration. For our field to produce rigorous, replicable research, researchers should strive to present protocols and data transparently (where possible) and collaborate to collect (multi-disciplinary) data as a collective effort.