Dr. Eggermann's research aims to understand the molecular basis of Russell-Silver syndrome, his laboratory utilises both clinical samples and molecular genetic tools to decipher the (epi)genotype-phenotype correlation.
Article first published online: 20 AUG 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Imprinted Genes and Human Disease
Volume 154C, Issue 3, pages 355–364, 15 August 2010
How to Cite
Eggermann, T. (2010), Russell–Silver syndrome. Am. J. Med. Genet., 154C: 355–364. doi: 10.1002/ajmg.c.30274
How to cite this article: Eggermann T. 2010. Russell–Silver Syndrome. Am J Med Genet Part C 153C:355–364.
- Issue published online: 20 AUG 2010
- Article first published online: 20 AUG 2010
- Else Kröner-Fresenius-Stiftung
- Russell–Silver syndrome;
- 11p15 epimutation;
- multilocus loss of methylation;
- genetic testing
In comparison to Prader–Willi or Angelman syndrome, Russell–Silver syndrome (RSS) is a relatively “young” imprinting disorder. This congenital disease is characterized by intrauterine and postnatal growth retardation, relative macrocephaly, a typical triangular face, asymmetry, and further less constant characteristic features. Genetic and epigenetic disturbances can meanwhile be detected in approximately 50% of patients with typical RSS features. Up to 5% of patients carry a maternal uniparental disomy of chromosome 7 (UPD(7)mat), at least 44% show hypomethylation in the chromosome 11p15 imprinting center 1 (IC). In 1–2% of RSS patients, (sub)microscopic chromosomal aberrations can be observed. The diagnostic workup should therefore include methylation/genomic testing for chromosome 11p15, UPD(7)mat analysis and molecular karyotyping. The recurrence risk is generally low in RSS but it can be strongly increased in cases of familial epimutations or a chromosomal rearrangement. Interestingly, in ∼7% of cases with chromosome 11p15 hypomethylation, hypomethylation of additional imprinted loci can be detected. Clinically, patients with hypomethylation at multiple loci do not differ from those with isolated 11p15 hypomethylation whereas the UPD(7)mat patients generally show a milder phenotype. Nevertheless, (epi)genotype–phenotype correlations are still evolving. Furthermore, the pathophysiological mechanisms resulting in the RSS phenotype still remain unknown despite the recent progress in deciphering the molecular defects associated with this condition. © 2010 Wiley-Liss, Inc.