2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Application of Prenatal Exome Sequencing in fetuses with Multiple Congenital Sonographic Abnormalities: A Report of Three Cases

Pdf Summary

This study reports on three cases where prenatal whole-exome sequencing (WES) was applied to fetuses with multiple congenital sonographic abnormalities. Case 1 involved a 32-year-old woman with a history of fetal death and recurrent fetal anomalies. Genetic analysis identified a homozygous ADAMTSL2 variant in both fetuses, expanding the phenotype of geleophysic dysplasia type 1. Case 2 involved a 35-year-old woman with abnormal third-trimester sonography. WES revealed a novel homozygous CNTNAP1 variant associated with lethal congenital contracture syndrome type 7. Case 3 involved an 18-week male fetus with multiple malformations. WES identified a de novo heterozygous CHD7 variant associated with CHARGE syndrome. The study highlights the clinical utility of prenatal trio-WES in diagnosing fetuses with structural abnormalities. <br /><br />Fetal structural abnormalities are present in 2-3% of pregnancies. WES, which focuses on coding regions of the genome, has improved diagnostic yield in children with unexplained genetic disorders. However, its use in prenatal settings is limited due to high costs, challenges in variant interpretation, and the inability to assess some phenotypic features. Despite these limitations, trio-WES has proven effective in cases with a history of prior affected and undiagnostic fetuses. <br /><br />In conclusion, this study demonstrates the value of prenatal trio-WES in diagnosing fetuses with multiple sonographic anomalies. The cases presented expand the understanding of certain genetic disorders and highlight the importance of genetic analysis in prenatal diagnosis.

Asset Subtitle

Presenting Author - Minh-Tuan HUYNH, MD PhD; Co-Author - Stéphanie Potel, Ms., MD; Co-Author - Sophie Degre, Ms, MD; Co-Author - Anne Panchout, Ms., Sage-femme; Co-Author - Cathy Bréon, Ms., Sage-femme; Co-Author - Detlef Trost, Mr., MD; Co-Author - Alexis Proust, Mr., Phd; Co-Author - Jérôme Bouligand, Mr., PharmaD, Professor; Co-Author - Anne-Claire Bréhin, Ms., MD; Co-Author - sophie Patrier-Sallebert, Ms., MD; Co-Author - Aicha Boughalem, Ms., MD;

Meta Tag

Congenital Anomaly

Dysmorphology

Exome sequencing

Genetic Testing

Genotype-Phenotype Correlations

NextGen Sequencing

Phenotype

Prenatal Diagnosis

Co-Author Stéphanie Potel, Ms., MD

Co-Author Sophie Degre, Ms, MD

Co-Author Anne Panchout, Ms., Sage-femme

Co-Author Cathy Bréon, Ms., Sage-femme

Co-Author Detlef Trost, Mr., MD

Co-Author Alexis Proust, Mr., Phd

Co-Author Jérôme Bouligand, Mr., PharmaD, Professor

Co-Author Anne-Claire Bréhin, Ms., MD

Co-Author sophie Patrier-Sallebert, Ms., MD

Co-Author Aicha Boughalem, Ms., MD

Presenting Author Minh-Tuan HUYNH, MD PhD

Keywords

prenatal whole-exome sequencing

fetuses

congenital sonographic abnormalities

geleophysic dysplasia type 1

lethal congenital contracture syndrome type 7

CHARGE syndrome

diagnosing fetuses

structural abnormalities

genetic disorders

prenatal diagnosis