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Oral Concurrent Session 3 - Ultrasound and Genetics

Oral Concurrent Sessions

Oral Concurrent Session 3 - Ultrasound and Genetics

(32) Genetic diagnoses in a national cohort with non-immune hydrops and other fetal effusions

Thursday, January 30, 2025

2:15 PM - 2:30 PM

Location: Aurora Ballroom CD, Lobby Level

Submitting Author and Presenting Author(s)

Natalie B. Gulrajani (she/her/hers)

University of California, San Francisco, School of Medicine
San Francisco, California, United States

Coauthor(s)

Billie R. Lianoglou, MS (she/her/hers)

Genetic Counselor
Center for Maternal-Fetal Precision Medicine, University of California San Francisco
San Francisco, California, United States
KT

Katie Tick

University of California, San Francisco
San Francisco, California, United States
NS

Nuriye Sahin-Hodoglugil, PhD

Program Manager
University of California, San Francisco
San Francisco, California, United States
UH

Ugur Hodoglugil, MD, PhD

Genomic Medicine Laboratory, University of California, San Francisco
San Francisco, California, United States
PD

Patrick Devine, MD, PhD

Genomic Medicine Laboratory, University of California, San Francisco
San Francisco, California, United States
JV

Jessica Van Ziffle, PhD

Genomic Medicine Laboratory, University of California, San Francisco
San Francisco, California, United States
Mary E. Norton, MD (she/her/hers)

Professor of Obstetrics, Gynecology & Reproductive Sciences
Center for Maternal-Fetal Precision Medicine, University of California San Francisco
San Francisco, California, United States
Teresa N. Sparks, MD, MS (she/her/hers)

Maternal-Fetal Medicine and Clinical Genetics
University of California, San Francisco
San Francisco, California, United States

Objective: Many single gene disorders are associated with non-immune hydrops fetalis (NIHF) and other fetal effusions. However, less is known about how these diseases present uniquely in utero. We aimed to characterize how genetic diseases present in utero with NIHF, other single effusions, and concurrent anomalies.

Study Design: This is a prospective national cohort of pregnancies with unexplained NIHF, pleural effusion, pericardial effusion, ascites, skin edema, cystic hygroma, increased nuchal translucency (NT) ≥3.5mm, or a combination of these. All ultrasound reports for each pregnancy were reviewed. A CLIA-approved laboratory performed exome sequencing (ES) and results were provided to patients. Each case was categorized as presenting with NIHF, single effusion (pleural or pericardial effusion, ascites, or skin edema), or increased NT or cystic hygroma, all with or without concurrent structural anomalies.

Results: 118 pregnancies underwent ES. There was a high diagnostic yield among cases with NIHF and single fetal effusions (17-36%), both with and without concurrent anomalies (Table 1). For cases with increased NT or cystic hygroma, the diagnostic yield was 42% for cases with concurrent anomalies, but zero in the absence of concurrent anomalies. Genetic diseases identified varied widely (Fig. 1). RASopathies, musculoskeletal disorders, and cardiomyopathies presented variably with and without concurrent anomalies and with all types of fetal effusions. Primary lymphedema syndromes presented later in gestation with NIHF and without concurrent anomalies. Diseases associated primarily with postnatal neurodevelopmental delay were seen with single fetal effusions and increased NT, with and without concurrent anomalies.

Conclusion: ES yielded a diagnosis in a high proportion of cases with NIHF and other single fetal effusions, with the exception of isolated increased NT or cystic hygroma. Certain genetic diseases presented broadly with all types of fetal effusions, while others presented more uniquely. Understanding these patterns informs accurate prenatal diagnosis, clinical counseling, and management.