Maternally inherited autosomal dominant PLAG‐1 related Silver Russell syndrome in a fetus with intra‐uterine growth restriction

Abstract

AbstractWe report a case of maternally inherited autosomal dominant PLAG‐1 related Silver Russell syndrome (SRS) in a fetus with IUGR and a mother who had growth and feeding problems in early life, dextrocardia and an atrio‐ventricular septal defect. Amniocentesis was performed due to marked intra‐uterine growth restriction (IUGR). The array was normal. Whole exome sequencing (WES) revealed a maternally inherited heterozygous likely pathogenic variant in PLAG1 (NM_002655.3): c.402delT p.(Gly135Aspfs*94). This variant has not been reported previously. PLAG1 pathogenic variants are associated with autosomal dominant Silver Russell syndrome, which fits with the clinical phenotypes of both fetus and mother. PLAG1 variants have previously been reported post‐natally in Silver Russell syndrome, but the phenotype tends to be milder than in 11p15.5 methylation‐related cases with fewer physical features. Although cardiac anomalies are uncommon in SRS, they have been previously reported. To our knowledge, dextrocardia has not been previously associated with SRS and there were no other potential causative genetic variants found. This report aims to highlight this rare type of SRS as a cause of IUGR.