Severe, rapidly progressive polyhydramnios with a structurally normal fetus remains a diagnostic challenge. We describe 2 consecutive pregnancies in the same mother that were complicated by massive polyhydramnios culminating in extreme preterm delivery and intra-uterine fetal demise. Trio whole-exome sequencing identified a previously unreported hemizygous MAGED2 variant (c.1330G>A; p.Gly444Ser), confirming antenatal Bartter syndrome (ABS, type V). This case underscores 3 practical messages: (1) an X-linked MAGED2 defect should be considered early when polyhydramnios recurs without anatomical anomalies and standard chromosomal microarray is normal; (2) timely genomic testing enables targeted counseling, antenatal management (eg, indomethacin) and discussion of pre-implantation diagnosis; and (3) dismissing genetic etiologies on the basis of mild maternal factors (eg, well-controlled gestational diabetes) risks missed diagnoses.
Engel et al. (Thu,) studied this question.