2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Microcephaly in Atypical Silver-Russell Syndrome Caused by Defects in<em> PLAG1</em>

Pdf Summary

This document discusses two cases of atypical Silver-Russell Syndrome (SRS) caused by defects in the PLAG1 gene. SRS is a genetic disorder characterized by growth failure and dysmorphic features. Inherited or de novo loss-of-function variants in the PLAG1 gene have been identified as a rare cause of SRS. The document presents two patients with different truncating (predicted loss-of-function) PLAG1 variants detected by whole-exome sequencing. Both patients exhibit intrauterine growth restriction (IUGR) and microcephaly, along with other clinical features such as short stature, failure to thrive, and abnormal facial features. The document suggests that PLAG1-related SRS represents an atypical presentation of the syndrome, with microcephaly as a discriminating feature. However, due to the limited number of reported cases, further studies are needed to understand the clinical characteristics and genetic correlations of PLAG1-related SRS. The document also provides information on the HMGA2-PLAG1-IGF2 pathway and its role in the development of SRS. Additionally, it mentions the genetic heterogeneity of SRS, with other causes including maternal uniparental disomy of chromosome 7 and pathogenic variants in genes such as IGF2, CDKN1C, HMGA2, and PLAG1. Overall, the document highlights the importance of expanding the phenotypic spectrum of SRS for accurate diagnosis and genetic counseling.

Asset Subtitle

Presenting Author - Wuyan Chen, PhD; Co-Author - Angela J. Gruber, PhD; Co-Author - McKenna Kyriss, PhD, FACMG; Co-Author - Eric Bend, PhD, FACMG; Co-Author - Rachel Sullivan, MSGC, CGC; Co-Author - Kim M. Keppler-Noreuil, MD, FACMG;

Meta Tag

Counseling

Exome sequencing

Genetic Testing

Genotype-Phenotype Correlations

Co-Author Angela J. Gruber, PhD

Co-Author McKenna Kyriss, PhD, FACMG

Co-Author Eric Bend, PhD, FACMG

Co-Author Rachel Sullivan, MSGC, CGC

Co-Author Kim M. Keppler-Noreuil, MD, FACMG

Presenting Author Wuyan Chen, PhD

Keywords

Silver-Russell Syndrome

PLAG1 gene

genetic disorder

growth failure

microcephaly

truncating PLAG1 variants

intrauterine growth restriction

clinical features

genetic heterogeneity

phenotypic spectrum