A new study in The New England Journal of Medicine used exome sequencing to analyze 127 fetuses with unexplained cases of nonimmune Hydrops fetalis.
Most fetal anomalies are not determined prenatally. Fluid buildup in fetuses, known as nonimmune Hydrops fetalis (NIHF), is no exception and can often be lethal.
A new study in The New England Journal of Medicine used exome sequencing to analyze 127 fetuses with unexplained cases of NIHF and identified a gene variant in approximately one-third of the cases.1
Researchers evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of the following conditions: fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions.
In 29% of the cases (37), researchers identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnosis); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others.
Overall, 68% of cases (25 of 37) with diagnostic variants were autosomal dominant, of which 12% were inherited and 88% were de novo. Ten of 37 (27%) were autosomal recessive, of which 95% were inherited and 5% were de novo. One was inherited X-linked recessive, and 1 was of uncertain inheritance.
Additionally, researchers identified potentially diagnostic variants in 12 additional cases.
Ob/gyns know that NIHF is often fatal and has several genetic causes. Exome sequencing is a rapid DNA sequencing technique that may be used to provide more in-depth information than current genetic testing methods.2
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The researchers were funded by the National Institutes of Health (NIH). Lead investigator Teresa Sparks, MD, of the University of California, San Francisco, is supported by a Women’s Reproductive Health Research grant from NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. Additional support was provided by the National Human Genome Research Institute.2