Genetic Testing in Newborns Moves From Rare to Routine Application

Newborns have at times been leaders and at others stragglers in the application of genetic testing. The onset of routine testing by the newborn screen in the 1950s heralded a new era in which presymptomatic testing for genetic diagnoses could enhance outcomes and in some cases even spare the child from developmental delay by the introduction of a special diet. In the 1970s, pioneering geneticists introduced cytogenetic analysis, which could detect aneuploidy, making the diagnosis of trisomy a routine adjunct of care. Subsequent advances in the method allowed high-resolution karyotype analysis and extended the utility to even small regions of the chromosome being deleted, duplicated, or rearranged. This was followed in the late 20th century by application of diagnosis-related tests based on fluorescence in situ hybridization or other specific assays, and now we have such tools as seizure panels. Microarray has also been an important contributor but with the introduction of whole-exome sequencing and even whole-genome sequencing, it is clear that up to one-third of disorders in the newborn period may be missed without the more comprehensive testing. All of the above methods are used in the situation of a rare phenotype seeking a diagnosis.