Prenatal diagnosis of autosomal recessive renal tubular dysgenesis caused by variants in the ACE gene: Two fetuses with anhydramnios

Abstract

Introduction: Autosomal recessive renal tubular dysgenesis (ARRTD) is a rare genetic disorder with a very high mortality rate. The typical symptoms of the disease during pregnancy are oligohydramnios, anhydramnios, and nearly all affected fetuses die after birth or have a stillbirth in late gestation, which can adversely increase maternal risks.

Methods: Oligohydramnios/anhydramnios can make both amniocentesis for diagnostic testing and morphological evaluation via ultrasound more difficult. In cases of oligohydramnios/anhydramnios suspicious for urinary tract anomalies, amnioinfusion is a meaningful technique that facilitates sampling of amniotic fluid for genetic diagnosis.

Results: We report two cases of fetuses with anhydramnios and invisible urinary bladder. Clinical exome sequencing from amniotic fluid revealed a biparentally inherited homozygous pathogenic nonsense ACE variant c.2503G 〉 T [p.Glu853Ter] in proband 1 and a biparentally inherited homozygous pathogenic nonsense ACE variant c.2992C 〉 T [p.Gln998Ter] in proband 2. The prognosis was poor and the patients elected to terminate the pregnancies. Additional post-mortem histopathological examination from the renal tissue of the second fetus showed renal tubular hypoplasia.

Conclusion: To our knowledge for the first time, we describe the prenatal diagnosis of ARRTD in Vietnam, and highlight the benefit of detecting ACE variants associated with ARRTD in fetuses with oligohydramnios/anhydramnios through amnioinfusion and amniocentesis, which improves genotype-phenotype correlations and provides valuable information for reproductive counseling.