Milestones and future perspectives in the discovery and treatment of HPDs with predisposition to HM. Although these disorders have been recognized phenotypically for decades, the advent and availability of NGS technologies have improved diagnosis, gene discovery, and understanding of disease progression in the last decade. We predict that with the development and accessibility of genomic technologies, including single-cell sequencing, PacBio optical genome mapping, the integration of artificial intelligence technologies, international standardization, and data sharing initiatives (ie, MatchMaker exchange and Shariant), and consortium-based projects to develop high-throughput functional studies (ie, Impact of Genomic Variation on Function [IGVF] Consortium, multiplexed assays of variant effect), this will rapidly advance the discovery of novel phenotypic-genotypic relationships in these disorders, identify novel pathogenic genes and disease mechanisms, and the much anticipated development of targeted therapies and clinical management guidelines for these patients. Created with BioRender.com. NIH, National Institutes of Health; WHO, World Health Organization.