Purpose of review: Antenatal Bartter's syndrome (aBS) is the most severe form of Bartter's syndrome, requiring close follow-up, in particular during the neonatal period, primarily because of prematurity. The recent identification of a novel and very severe form of aBS merits an update on this topic.
Recent finding: Despite the identification of several genes involved in Bartter's syndrome, about 20% of patients clinically diagnosed with aBS remained without genetic explanation for decades. We recently identified mutations in MAGED2 as a cause of an X-linked form of aBS characterized by a very early onset of severe polyhydramnios and extreme prematurity leading to high mortality. Remarkably, all symptoms in surviving patients with MAGE-D2 mutations resolve spontaneously, within weeks after preterm birth. Interestingly, MAGE-D2 affects the expression of the sodium chloride cotransporters NKCC2 and NCC, explaining thereby the severity of the disease. Importantly, a more recent analysis of MAGED2 in a large French cohort of patients with aBS confirmed our data and showed that females can also be affected.
Summary: MAGE-D2 is critical for renal salt reabsorption in the fetus, amniotic fluid volume regulation, and maintenance of pregnancy. Most importantly, MAGED2 must be included in the genetic screening of every form of aBS.