Abstract
INTRODUCTION: Vein of Galen malformation (VGM) results from an aneurysmal aberration with an arteriovenous shunting of blood and is the most frequent arteriovenous malformation in infants and fetuses. The congenital malformation develops during weeks 6-11 of fetal development. Infants often die from high-output congestive heart failure. VGM is mostly considered as a sporadic condition with minimal recurrence risk in subsequent pregnancies. Mendelian forms of VGM have rarely been described as infrequent phenotypic presentations of 2 disorders: capillary malformation-arteriovenous malformation syndrome (RASA1, EPHB4) and hereditary hemorrhagic telangiectasia (ENG, ACVRL1, and SMAD4), both showing autosomal dominant inheritance. CASE PRESENTATION: Here, we report on a consanguineous couple with recurrent VGM in 2 pregnancies. Both partners were found to be affected by hereditary hemorrhagic telangiectasia due to a known pathogenic heterozygous c.790G>A (p.Asp264Asn) variant in ENG. Fetal DNA was unavailable, however in view of the mild phenotype in the couple, along with the severe prenatal presentation in 2 pregnancies, the fetus was presumed to be homozygous for the ENG variant. A subsequent pregnancy revealed a fetus heterozygous for the variant, which had an uneventful perinatal course. CONCLUSION: This report highlights a severe perinatal lethal phenotype due to biallelic variants in a gene hitherto known to cause an autosomal dominant disorder.