Epigenetic and genetic diagnosis of Silver–Russell syndrome

Abstract

Silver–Russell syndrome (SRS) is a congenital imprinting disorder characterized by intrauterine and postnatal growth restriction and further characteristic features. SRS is genetically heterogenous: 7–10% of patients carry a maternal uniparental disomy of chromosome 7; >38% show a hypomethylation in imprinting control region 1 in 11p15; and a further class of mutations are copy number variations affecting different chromosomes, but mainly 11p15 and 7. The diagnostic work-up should thus aim to detect these three molecular subtypes. Numerous techniques are currently applied in genetic SRS testing, but none of them covers all known (epi)mutations, and they should therefore be used synergistically. However, future next-generation sequencing approaches will allow a comprehensive analysis of all types of alterations in SRS.

Keywords::

• aberrant methylation
• epimutation
• genetic testing
• Silver–Russell syndrome
• uniparental disomy

Financial & competing interests disclosure

The authors are supported by the Bundesministerium für Bildung und Forschung (Network ‘Imprinting Diseases’, 01GM0884). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.