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Counseling Challenges with Variants of Uncertain Significance and Incidental Findings in Prenatal Genetic Screening and Diagnosis

Overview
Journal J Clin Med
Specialty General Medicine
Date 2015 Aug 4
PMID 26237491
Citations 34
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Abstract

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.

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References
1.
Fiorentino F, Caiazzo F, Napolitano S, Spizzichino L, Bono S, Sessa M . Introducing array comparative genomic hybridization into routine prenatal diagnosis practice: a prospective study on over 1000 consecutive clinical cases. Prenat Diagn. 2011; 31(13):1270-82. DOI: 10.1002/pd.2884. View

2.
Breman A, Pursley A, Hixson P, Bi W, Ward P, Bacino C . Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature. Prenat Diagn. 2012; 32(4):351-61. DOI: 10.1002/pd.3861. View

3.
Shaffer L, Dabell M, Fisher A, Coppinger J, Bandholz A, Ellison J . Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies. Prenat Diagn. 2012; 32(10):976-85. PMC: 3491694. DOI: 10.1002/pd.3945. View

4.
Pan M, Li F, Li Y, Jiang F, Li D, Lau T . Discordant results between fetal karyotyping and non-invasive prenatal testing by maternal plasma sequencing in a case of uniparental disomy 21 due to trisomic rescue. Prenat Diagn. 2013; 33(6):598-601. DOI: 10.1002/pd.4069. View

5.
. ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011; 117(4):1028-1031. DOI: 10.1097/AOG.0b013e31821922c2. View