Prenatal and molecular characteristics of 23 cases with Silver-Russell syndrome

Introduction To date, only case reports regarding prenatal diagnosis of Silver-Russell syndrome (SRS) have been documented in the literature. In this study, we aim to elucidate the prenatal characteristics associated with SRS along with their molecular aspects. Methods This was a retrospective study of 23 cases with SRS. All cases received either prenatal or postnatal diagnoses of SRS with molecular confirmation harboring disease-causing defects in the mechanisms known to be associated with SRS. The medical records of patients were meticulously collected and reviewed. Results Of the 12 prenatally diagnosed cases, seven were identified due to intrauterine growth restriction (IUGR), two were detected following positive non-invasive prenatal testing results indicating trisomy 7, and three diagnoses were prompted by advanced maternal age. Of the 11 postnatally diagnosed cases, all exhibited IUGR in utero. Among all 18 cases presenting with IUGR, four were classified as early-onset IUGR, while the remaining 14 were diagnosed in the third trimester. Maternal uniparental disomy 7 accounted for the molecular defect in SRS in fifteen instances, followed by loss of imprinting center 1 methylation at 11p15 in five instances and maternal duplication of chromosome region 11p15.5 in another three instances. Conclusion Our findings highlight the significance of IUGR as a prenatal marker for SRS. Targeted molecular testing for SRS, including methylation-specific assays at key imprinted loci, should be integrated into the standard genetic evaluation of fetuses with unexplained IUGR.