Hydrops fetalis corresponds to the accumulation of fluid in soft tissues and/or body cavities. Hydrops fetalis is classified as immune (IFH) and non-immune (NIFH). NIFH can be secondary to multiple etiologies: aneuploidy, congenital heart disease, and various monogenic disorders.The prenatal exome increases the diagnostic yield by 3-19% in cases of NIFH with normal karyotype and microarray, if isolated or associated with other anomalies, respectively. Aberrant development of the lymphatic system has been associated with more than 20 genetic variants, one of them in the PIEZO1 gene that produces two diseases: hereditary dehydrated stomatocytosis and lymphatic malformation 6, both conditions related to NIFH with similar phenotypes. We report a case of NIFH with normal conventional cytogenetic study in which a prenatal exome study was performed identifying a pathogenic variant in PIEZO1 gene allowing to establish that both conditions have a favorable perinatal prognosis.The prenatal exome study of NIFH with normal karyotype is widely justified, despite its high cost and low accessibility in our setting, to stablish the perinatal prognosis and adequately advise parents in terms of recurrence.