Category: Genetics
Poster Session II
Non-immune hydrops fetalis is genetically and physiologically heterogenous. We sought to describe rare genetic diagnoses presenting with hydrops or fetal effusions and possible fetal anemia that may be amenable to in utero transfusions (IUT).
Study Design:
Retrospective review of cases of NIHF or fetal effusions that underwent genetic testing at our institution. Included cases had a pathogenic or likely pathogenic variant on exome sequencing (ES) or microarray, with either elevated middle cerebral artery (MCA) Dopplers or results that implicated a genetic disease associated with anemia. Demographics, sonograms, genetic test results, and neonatal and delivery outcomes were abstracted for each case. All sonograms were performed at a tertiary care referral center and interpreted by a Maternal-Fetal-Medicine specialist or Radiologist.
Results:
We identified 8 cases of prenatally diagnosed single gene disorders that presented with NIHF or fetal effusions, including skin edema (7/8), pericardial effusion (6/8), pleural effusion (4/8), ascites (5/8) and polyhydramnios (3/8). Elevated (MCA) Doppler (5/8) was seen in most cases. Variants in PIEZO1 (3), RPL11, HBA2, ANKRD1, and NPC1 as well as RPL15 full gene deletion were classified as likely pathogenic or pathogenic by American College of Medical Genetics guidelines. Two cases resulted in termination and 2 chose comfort care; the other four patients survived to hospital discharge. IUT was performed in four cases, two survivors (diagnosis of dehydrated hereditary stamatocytosis and KBG syndrome) and both cases who chose comfort care (diagnosis of Diamond Blackfan Anemia and Niemann-Pick Disease, Type C).
Conclusion:
Our data support the utility of comprehensive genetic work-up for NIHF spectrum with microarray and exome sequencing to identify genetic conditions potentially amenable to IUT. These data highlight rare single gene disorders as potential indications for IUT: While fetal anemia has not been described with variants in NPC1 and ANKRD11, these cases may represent phenotype expansion.
Billie R. Lianoglou, MS
Genetic Counselor
University of California, San Francisco
San Francisco, California, United States
Sarah L. Downum, BS
Clinical Research Coordinator, Pre-med student
University of California, San Francisco
San Francisco, California, United States
Juan Gonzalez Velez, MD, PhD (he/him/his)
Associate Professor, Obstetrics, Gynecology & Reproductive Sciences
UCSF School of Medicine
San Francisco, California, United States
Angie Jelin, MD
Associate Professor
Johns Hopkins University School of Medicine, Department of Gynecology and Obstetrics
Baltimore, Maryland, United States
Mara Rosner, MD, MPH
Assistant Professor
Johns Hopkins Center for Fetal Therapy
Baltimore, Maryland, United States
Mary E. Norton, MD
Division Chief, MFM, Dept of Obstetrics, Gynecology & Reproductive Sciences
University of California, San Francisco
San Francisco, California, United States
Teresa N. Sparks, MD, MAS
Maternal-Fetal Medicine and Clinical Genetics
University of California, San Francisco
San Francisco, California, United States