Clinically Distinct Epigenetic Subgroups in Silver-Russell Syndrome: The Degree of<i>H19</i>Hypomethylation Associates with Phenotype Severity and Genital and Skeletal Anomalies

We found a dose-response relationship between the degree of H19 hypomethylation and phenotype severity in SRS. We report for the first time the association of specific anomalies of the spine, elbows, hands and feet, and genital defects in SRS with severe H19 hypomethylation. Classical SRS features were found in H19 hypomethylation and milder symptoms in maternal uniparental disomy of chromosome 7, thus distinguishing two separate clinical and etiological subgroups.