For almost everyone born in the U.S., newborn screening provides the first exposure to genomic testing. The “universal” screening panel recommended by the Secretary’s Advisory Committee for Heritable Diseases of Newborns and Children includes over 50 conditions, of which most are heritable.69 Traditionally, newborn screening assays utilize biochemical testing for metabolites, proteins, or enzymatic activity. Recently, incorporating next generation sequencing into newborn screening has been considered. The rationale for integration is that additional information from sequencing can augment biochemical data for conditions already on the universal newborn screening panel by pinpointing the causal genetic variation, while also increasing greatly the number of conditions detected prior to onset of symptoms. Another potential benefit is that sequence data obtained in the newborn period could be available to inform care across the individual’s lifespan. Given the number of newborns involved and the need in this setting for rapid turn-around of highly accurate sequence interpretation, sequence-based newborn screening might have seemed fantastical five years ago, but recent studies suggest that technical feasibility may not be far off.70 The practicalities of implementing sequencing in the
