# Prenatal diagnosis of Silver–Russell syndrome with 8q12 deletion including the PLAG1 gene: a case report and review

## TL;DR

This case report describes the first prenatal diagnosis of Silver–Russell syndrome caused by a deletion in the PLAG1 gene, offering new insights into its genetic and clinical features.

## Contribution

The first prenatal case of PLAG1-related Silver–Russell syndrome is reported, expanding understanding of its genetic basis and phenotypic variability.

## Key findings

- A prenatal case of Silver–Russell syndrome with an 8q12 deletion involving the PLAG1 gene was identified.
- The fetus showed intrauterine growth retardation, macrocephaly, and micrognathia but lacked body asymmetry.
- The case contributes to genotype–phenotype correlations in rare PLAG1-related SRS cases.

## Abstract

Silver–Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder. A retrospective analysis predicted that the live birth prevalence of SRS in Estonia is 1:15,886 [Yakoreva et al., Eur J Hum Genet, 2019, 27(11), 1649–1658]. The most common causative genetic mechanism in the proband is loss of paternal methylation in the imprinted control region 1 (ICR1) at 11p15.5 chromosome. A few studies suggested that inherited or de novo loss-of-function alterations of the PLAG1 gene, including the whole-gene deletion and intragenic pathogenic variants, could cause a rare type of SRS. To date, less than 20 unrelated PLAG1-related SRS cases have been reported, and the clinical information about these cases is limited. We report the first prenatal case of SRS with 8q12 deletion (including the PLAG1 gene). The fetus presented with intrauterine growth retardation, small for gestational age, relative macrocephaly at birth, and a protruding forehead. Unlike classical SRS cases, the fetus had micrognathia and did not show body asymmetry. We hope that the literature review in this study provides new insights into genotype–phenotype relationships of PLAG1-related SRS.