Counseling Challenges with Variants of Uncertain Significance and Incidental Findings in Prenatal Genetic Screening and Diagnosis
Overview
Affiliations
Prenatal genetic screening and testing provides prospective parents information about the health of their fetus. It is offered to find or address an increased risk for chromosomal abnormalities or other genetic conditions in the fetus or to identify the cause of fetal structural abnormalities detected by prenatal imaging. Genome-wide tests, such as the already widely-used chromosomal microarray analysis and emerging diagnostic whole exome and whole genome sequencing, have improved the ability to detect clinically significant findings, but have also increased the chance of detecting incidental findings and variants of uncertain significance. There is an extensive ongoing discussion about optimal strategies for diagnostic laboratories to report such findings and for providers to communicate them with patients. While consensus opinions and guidelines are beginning to appear, they often exclude the prenatal setting, due to its unique set of challenging considerations. These include more limited knowledge of the impact of genetic variants when prospectively detected in an ongoing pregnancy, the absence or limitations of detecting clinically recognizable phenotypes at the time of testing and the different decision-making processes that will ensue from testing. In this review, we examine these challenges within the medical ethical framework unique to prenatal care.
Li S, Chen L, Deng C, Tang D, Zhang J, Hu W BMC Pregnancy Childbirth. 2024; 24(1):865.
PMID: 39725884 PMC: 11674561. DOI: 10.1186/s12884-024-07052-3.
Phenotype driven molecular genetic test recommendation for diagnosing pediatric rare disorders.
Chen F, Ahimaz P, Nguyen Q, Lewis R, Chung W, Ta C NPJ Digit Med. 2024; 7(1):333.
PMID: 39572625 PMC: 11582592. DOI: 10.1038/s41746-024-01331-1.
Pynaker C, McCoy J, Halliday J, Lewis S, Amor D, Walker S BMC Pediatr. 2024; 24(1):536.
PMID: 39174956 PMC: 11340052. DOI: 10.1186/s12887-024-05012-6.
Fortin O, Mulkey S, Fraser J Pediatr Res. 2024; .
PMID: 38937640 DOI: 10.1038/s41390-024-03343-9.
Peter M, Mellis R, McInnes-Dean H, Daniel M, Walton H, Fisher J Front Genet. 2024; 15:1401705.
PMID: 38903755 PMC: 11188373. DOI: 10.3389/fgene.2024.1401705.