Rare Genetic Diseases in the Era of Genomics: Diagnosis, Pathogenesis, and the Road to Treatment

Rare genetic diseases — individually uncommon but collectively affecting hundreds of millions of individuals worldwide — represent one of the greatest challenges and opportunities in modern medicine, and this chapter reviews the molecular underpinnings, diagnostic journey, and emerging therapeutic landscape across a spectrum of rare monogenic and chromosomal conditions. It examines how whole-genome sequencing and multi-omics approaches have dramatically increased the diagnostic yield in rare disease cohorts, and reviews the development of gene therapy, gene editing, and small molecule strategies for conditions previously considered untreatable. The chapter concludes with a discussion of the ethical, regulatory, and health equity dimensions of rare disease research and care.