2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Congenital anemias in nonimmune hydrops fetalis diagnosed by exome sequencing

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This study aimed to review the spectrum of congenital anemias diagnosed by exome sequencing (ES) in cases of nonimmune hydrops fetalis (NIHF) and describe the prenatal phenotype of these congenital anemias. A systematic review of ES studies for NIHF was conducted, and all congenital anemia gene variants reported in cases that met phenotypic criteria for NIHF were recorded. The diagnostic yield of ES for congenital anemia in NIHF was found to be 3%. Congenital anemias diagnosed by ES in NIHF manifested as isolated NIHF. The study identified several gene variants associated with different types of congenital anemias, such as SEC23B, KLF1, RFWD3, UNC13D, RPL11, and SPTA1. Of the 188 cases with a genetic diagnosis, six were attributed to congenital anemias. The majority of variants were inherited, with a recurrence risk of 25%. Some variants were de novo, and one case was compound heterozygous. Most cases of congenital anemia in NIHF were isolated, except for two cases that had additional phenotypic features like clenched hypeflexed hands and absent stomach bubble. Among the pregnancies resulting in live births, there was a high mortality rate. The study concludes that NIHF due to congenital anemias can have poor outcomes, and genetic counseling is recommended to discuss recurrence risks and options for prenatal diagnosis. Overall, congenital anemias accounted for 3% of NIHF cases diagnosed by ES.

Asset Subtitle

Presenting Author - Mona M. Makhamreh, MD; Co-Author - Kavya Shivashankar, MD; Co-Author - Stephanie Rice, MS, CGC; Co-Author - Casey J. Brewer, PhD; Co-Author - Hiba Mustafa, MD; Co-Author - Seth I. Berger, MD, PhD; Co-Author - Huda B. Al-Kouatly, MD, FACOG, FACMG;

Meta Tag

Prenatal Diagnosis

Co-Author Kavya Shivashankar, MD

Co-Author Stephanie Rice, MS, CGC

Co-Author Casey J. Brewer, PhD

Co-Author Hiba Mustafa, MD

Co-Author Seth I. Berger, MD, PhD

Co-Author Huda B. Al-Kouatly, MD, FACOG, FACMG

Presenting Author Mona M. Makhamreh, MD

Keywords

congenital anemias

exome sequencing

nonimmune hydrops fetalis

prenatal phenotype

gene variants

diagnostic yield

isolated NIHF

recurrence risk

genetic counseling

mortality rate