N-of-1 genomic medicine for the rare pediatric genetic diseases

Introduction: The era of genomic medicine has commenced. Contiguous genome information promises to change the practice of medicine markedly. Inherent to genomic medicine is the concept of personalized treatments informed both by an individual's molecular disease and by genetic variants that alter their responses to relevant therapeutic interventions. Although genome information is growing in importance in molecular treatment of cancer and pharmacogenomics as applied to drug-metabolism, it has infrequently been applied to ultra-rare, monogenetic disorders. Areas covered: The published literature on design and implementation of N-of-1 studies in rare diseases and pediatric genomic medicine is reviewed (PubMed, OVID Medline and Cochrane databases with terms 'N-of-1', 'N-of-1 clinical trial', 'inborn error of metabolism', 'genetic disorders', 'genetic syndromes', and 'treatment of genetic disorders'), with extension of methods to the practice of genomic medicine. Expert opinion: Case studies are often ignored in evidence-based medicine protocols. This review specifically addresses the concept that individualized, genome-informed treatments for ultra-rare genetic disorders are quintessentially N-of-1 clinical studies.