2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Trends in Prenatal Genetic Diagnosis for Congenital Diaphragmatic Hernia: A 20-Year Single Center Retrospective Review

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A 20-year retrospective review of prenatal genetic diagnostics for congenital diaphragmatic hernia (CDH) was conducted at a single referral center. The study found that invasive prenatal testing, such as chorionic villus sampling (CVS) and amniocentesis, has declined significantly in fetuses with CDH. The decline began in 2013, coinciding with the widespread adoption of noninvasive prenatal screening (NIPS) using cell-free DNA (cfDNA) testing. Prior to the adoption of NIPS, most diagnoses were made through invasive procedures, but only one diagnosis was made following abnormal cfDNA screening.<br /><br />CDH is a common birth defect with significant morbidity and mortality. It has various genetic etiologies, including aneuploidies, structural chromosomal anomalies, and monogenic disorders. Cytogenetic testing, such as karyotype and chromosomal microarray analysis (CMA), has a diagnostic yield of approximately 10%, while sequencing techniques, such as whole exome sequencing, have a yield of up to 30-40% when additional anomalies are present.<br /><br />The study found that cfDNA screening alone is of limited clinical utility in the prenatal diagnosis of CDH. Forgoing invasive prenatal testing often delays genetic diagnosis until the postnatal period. However, earlier diagnosis could have implications for prenatal and postnatal management.<br /><br />The results highlight the importance of consistently counseling about the risks and benefits of genetic testing in fetuses with congenital anomalies. Noninvasive screening technologies, such as targeted sequencing and whole exome sequencing using cfDNA, may be attractive alternatives for cases where invasive prenatal testing is declined.<br /><br />The study analyzed a cohort of 373 CDH fetuses, with the majority being isolated/nonsyndromic cases. The pregnancy outcomes included termination, fetal demise, and live birth.<br /><br />In terms of genetic diagnoses, the study compared prenatal and postnatal testing results. Cytogenetics provided the majority of diagnoses, while sequencing techniques identified specific conditions such as Cornelia de Lange syndrome and Kabuki syndrome, among others.<br /><br />Overall, the study demonstrates the changing landscape of prenatal genetic diagnosis for CDH, with a decline in invasive testing and increased adoption of noninvasive screening methods.

Asset Subtitle

Presenting Author - Sarah L. Bick, MD; Co-Author - Jennifer M. Lyu, MS; Co-Author - Tabitha A. Poorvu, MS, LCGC; Co-Author - Patricia K. Donahoe, MD; Co-Author - Jill M. Zalieckas, MD, MPH; Co-Author - Kathryn J. Gray, MD, PhD; Co-Author - David Zurakowski, PhD; Co-Author - Frances A. High, MD, PhD; Co-Author - Terry L. Buchmiller, MD;

Meta Tag

Cell free DNA/cfDNA

Congenital Anomaly

Genetic Testing

Prenatal Diagnosis

Co-Author Jennifer M. Lyu, MS

Co-Author Tabitha A. Poorvu, MS, LCGC

Co-Author Patricia K. Donahoe, MD

Co-Author Jill M. Zalieckas, MD, MPH

Co-Author Kathryn J. Gray, MD, PhD

Co-Author David Zurakowski, PhD

Co-Author Frances A. High, MD, PhD

Co-Author Terry L. Buchmiller, MD

Presenting Author Sarah L. Bick, MD

Keywords

prenatal genetic diagnostics

congenital diaphragmatic hernia

invasive prenatal testing

noninvasive prenatal screening

cell-free DNA testing

cytogenetic testing

cfDNA screening

genetic diagnosis

postnatal management

genetic testing