HYDROPS FETALIS

Overview

Hydrops fetalis occurs in approximately 1 in 1,700 to 1 in 3,000 pregnancies, with over 90% of cases being non-immunological in nature. The condition is characterized by fluid accumulation in at least two fetal compartments. Genetic diagnostics, which usually include chromosome analysis and exome analysis, identify Turner syndrome and Noonan syndrome as the most common causes, but despite extensive testing, the cause remains unclear in 15 to 25% of cases. Diagnosis is complicated by the often nonspecific phenotype in the prenatal setting.

Symptoms

It is defined as an accumulation of fluid in at least two fetal compartments: subcutaneous (>5mm), pericardial, pleural and abdominal (ascites).

Frequency

Hydrops fetalis is observed in approximately one in every 1,700 to 3,000 pregnancies, with non-immune hydrops (NIHF) now accounting for over 90% of cases.

Cause

In addition to exogenous causes, hydrops fetalis can be caused by over 150 mostly rare genetic disorders; genetic testing should therefore be conducted on a correspondingly broad basis. This is usually done by diagnostic puncture and includes a chromosome analysis and/or a chromosomal microarray and, if normal, a molecular genetic test, which in turn should include a Noonan syndrome or RASopathy panel. The most common chromosomal disorder is Turner syndrome (45,X); the most common monogenic cause is Noonan syndrome. Furthermore, numerous metabolic disorders (probably >15%), especially lysosomal storage disorders, more common (alpha-thalassemia) and rare anemias, skeletal dysplasias, muscular, urogenital and cardiovascular diseases are possible causes. Even with extensive genetic testing, the cause of around 15 to 25% of NIHF cases remains unknown.

The difficulty in the prenatal setting is that the phenotype is often completely unspecific and therefore does not provide any additional information when evaluating large panels or even an exome analysis.

References

Mardy et al. 2019, Prenatal Diagnosis 39:732 / Laterre et al. 2018, Prenat Diagn 38:337 / Sudrié-Arnaud et al. 2018, Clin Chim Acta 481:1 / Best et al. 2018, Prenat Diagn 38:10 / International Society for Prenatal Diagnosis, Society for Maternal and Fetal Medicine, Perinatal Quality Foundation. Joint position statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn 2018; 38:6 / Bellini et al. 2015, Am J Med Genet 167A:1082