Twin‐twin transfusion syndrome recipient with arterial calcification and heterozygous variant in ABCC6: Evidence of a gene‐environment interaction?

Abstract

We report a case of a twin-twin transfusion syndrome (TTTS) recipient who, after successful fetoscopic surgery, developed a large pericardial effusion and calcifications of the aorta and main pulmonary artery. The donor fetus never had cardiac strain and never developed cardiac calcifications. A heterozygous likely pathogenic variant in ABCC6 (c.2018T > C, p.Leu673Pro) was identified in the recipient twin.While TTTS recipient twins are at risk of arterial calcifications and right heart failure secondary to the disease, calcifications of the great vessels are also observed in generalized arterial calcification of infancy, a Mendelian genetic disorder with associated biallelic pathogenic variations in ABCC6 or ENPP1, which can result in significant pediatric morbidity or mortality. The recipient twin in this case had some degree of cardiac strain prior to TTTS surgery; however, the progressive calcification of the aorta and pulmonary trunk occurred weeks after TTTS resolution. This case raises the possibility of a gene-environment interaction and emphasizes the need for genetic evaluation in the setting of TTTS and calcifications. Key points What's already known about this topic?� Recipient cardiomyopathy is a feature of twin-twin transfusion syndrome (TTTS). Pathogenic compound heterozygosity and homozygosity in ABCC6 can lead to general arterial calcifications of infancy, a rare and potentially lethal disease. What does this study add?� TTTS in combination with heterozygosity in ABCC6 led to numerous arterial calcifications in utero without significant pediatric disease.Andrea Springman and Braxton Forde contributed equally and share primary authorship of this report.