Fetal Hydrops: Genetic Dissection of an Unspecific Sonographic Finding-A Comprehensive Review

Fetal hydrops is defined as the presence of abnormal fluid collections in two or more intra-fetal compartments. It has been classified based on etiology (immune vs. non-immune), on the presence or absence of other findings (isolated vs. non-isolated) and on the gestational age at presentation (first-, second- or third-trimester). In all cases of non-immune hydrops fetalis, invasive prenatal diagnosis is offered. However, after cytogenetic analyses, 80% of fetuses remain without etiological diagnosis, not allowing one to define the prognosis and to formulate recurrence risks. Several geneticists recommend performing either a next-generation sequencing panel (commonly limited to RASopathy testing) or exome sequencing, if cytogenetic tests are inconclusive. In the literature, the data are extremely heterogeneous, due to the differences in these indications and the limitation of study to a select group of genes. The identification of the underlying cause is crucial, as prognostic information and even therapy options are becoming increasingly available for a wide and growing array of genetic conditions. A systematic approach would allow an overall evaluation of the diagnostic rate of the exome sequencing in fetal effusions, also calculating the prevalence of associated diseases, with the aim of obtaining a diagnosis, defining the most appropriate management for each case, and broadening the spectrum of conditions known to be associated with hydrops.