Anhydramnios, but prenatally normal kidneys: renal tubular dysgenesis – patient with mutations in the renin-angiotensin system gene AGTR1

Abstract

BackgroundPrenatally detected oligo- or even anhydramnios may – beside other reasons – be indicative for a diminished or absent urine production. The resulting clinical picture is a “Potter sequence” with arthrogrypotic joint contractions, a flat face and most importantly pulmonary hypoplasia. In severe cases this pulmonary hypoplasia can be life-limiting irrespective of the underlying lesion.Case presentationOur patient initially presented with anhydramnios and normal kidneys at external ultrasonography after 31 weeks of pregnancy. Following spontaneous birth after 37 weeks of gestation, the baby boy was born with all the clinical signs of a “Potter-sequence” along with a severe pulmonary hypoplasia leading to insufficient oxygenation and ventilation. Despite all measures taken, the child died after 8 h of life. Beside life-limiting pulmonary hypoplasia postmortem examination again confirmed macroscopically normal kidneys, but microscopy showed compact and variable sized glomeruli, numerically reduced and immature tubules, a structurally altered renal vascular bed and an expanded medullar interstitium. Immunohistochemical studies revealed the absence of proximal convoluted tubules, shortened proximal straight tubules beside an immaturity and dysmorphogenesis of the other segments of the nephron, and thus proved renal tubular dysgenesis (RTD) as the underlying disease. A homozygous mutation c.377G>C (p.Arg126Pro) in exon 2 of the AGTR1 gene was found, leading to the exchange of a highly conserved arginine to proline. This mutation has not been reported in public databases so far. As expected, both consanguineous parents were heterozygous for this mutation.ConclusionRTD has to be considered in an anuric fetus with apparently normal renal sonography in order to allow adequate prenatal counseling and – if indicated – palliative postnatal care.