Challenges and Pragmatic Solutions in Pre-Test and Post-Test Genetic Counseling for Prenatal Exome Sequencing

Abstract

Karin EM Diderich, Jasmijn E Klapwijk, Vyne van der Schoot, Hennie T Brüggenwirth, Marieke Joosten, Malgorzata I Srebniak Department of Clinical Genetics, Erasmus MC, Rotterdam, the NetherlandsCorrespondence: Karin EM Diderich, Department of Clinical Genetics, Erasmus MC, Wytemaweg 50, Rotterdam, the Netherlands, Tel [phone], Email [email protected]: The yield of genetic prenatal diagnosis has been notably improved by introducing whole genome chromosomal microarray (CMA) and prenatal exome sequencing (pES). However, together with increased numbers of diagnoses made, the need to manage challenging findings such as variants of unknown significance (VUS) and incidental findings (IF) also increased. We have summarized the current guidelines and recommendations and we have shown current solutions used in our tertiary center in the Netherlands. We discuss four of the most common clinical situations: fetus with normal pES results, fetus with a pathogenic finding explaining the fetal phenotype, fetus with a variant of uncertain clinical significance fitting the phenotype and fetus with a variant leading to an incidental diagnosis. Additionally, we reflect on solutions in order to facilitate genetic counseling in an NGS-era.Keywords: exome sequencing, genetic counseling, prenatal diagnosis, incidental findings, variants of unknown significance, VUS, IF

Keywords

• exome sequencing
• genetic counseling
• prenatal diagnosis
• incidental findings
• variants of unknown significance