Prenatal genomic testing for ultrasound detected fetal structural anomalies

Key content In the presence of a fetal structural anomaly, fetal DNA can be obtained through invasive testing (e.g. amniocentesis and chorionic villus sampling) in order to undertake genomic testing to attempt to uncover a unifying genetic diagnosis. There are number of traditional and more novel genomic tests available, which can identify aneuploidy, chromosomal structural variation and/or sequence variants within genes. The cumulative diagnostic yield of such technologies is approximately 25%, 6% and up to 80% in some cohorts for QF-PCR/G-banding karyotype, chromosome microarray and exome sequencing, respectively. Learning objectives To understand the technical basis and clinical indications for QF-PCR, G-banding karyotype, chromosome microarray and exome sequencing. To appreciate the potential benefits and challenges associated with exome sequencing. To gain awareness of modern technologies that may be utilised to address recurrence risk, e.g. preimplantation genetic diagnosis and non-invasive prenatal diagnosis. Ethical issues Not all technologies are currently available across all four nations of the UK, hence challenges are raised regarding healthcare equity. There can be uncertainty around the interpretation of prenatal genomic test results, which can have implications in counselling, particularly regarding termination of pregnancy. Incidental findings may be revealed, which can have implications for counselling and the future health of the fetus and the parents.