ABSTRACT
Advances in DNA technology that have occurred since the completion of the Human Genome Project mean that an increasing number of single gene disorders have become amenable to genetic diagnosis, including in a prenatal setting. Recently, the introduction of next-generation sequencing (NGS) provides the ability to screen for a large number of conditions when a genetic diagnosis is suspected, but a precise disorder is not evident. When prenatal exome sequencing is used in the setting of one or more fetal anomalies, the reported yield varies widely, from 5-50%. While exome sequencing can be useful in many circumstances, clinicians ordering and interpreting genomic sequence tests should appreciate that a genetic test that reports a pathogenic variant is not equivalent to diagnosing the patient with the associated disorder. Rather, the genetic test result should be integrated with the clinical characteristics and family history of the patient to arrive at a clinical-molecular diagnosis. Undoubtedly, gene panels, exome sequencing, and eventually whole genome sequencing will increasingly be applied to evaluation of fetal anomalies. NGS has the potential to greatly advance prenatal diagnosis but is complicated by the complexity of available tests. The optimal testing strategy requires expertise, and these tests should be used in consultation with genetic specialists.
