New developments in Silver-Russell syndrome and implications for clinical practice

Area of Science:

• Genetics
• Epigenetics
• Developmental Biology

Background:

• Silver-Russell syndrome (SRS) is a heterogeneous imprinting disorder characterized by growth restriction, relative macrocephaly, and distinctive facial features.
• It arises from aberrant gene expression due to epigenetic defects.
• Known genetic causes include maternal uniparental disomy of chromosome 7 (~10%) and hypomethylation at chromosome 11p15.5 (~50%), leaving many cases unexplained.

Purpose of the Study:

• To comprehensively review all reported molecular defects in Silver-Russell syndrome.
• To underscore the necessity of multi-locus/tissue testing and trio screening.
• To discuss epigenetic and phenotypic overlaps with other imprinting disorders.

Main Methods:

• Literature review of reported molecular defects in Silver-Russell syndrome.
• Analysis of genetic and epigenetic causes, including uniparental disomy and imprinting control region abnormalities.
• Comparative analysis of phenotypic and epigenetic features with other imprinting disorders.

Main Results:

• A comprehensive list of molecular defects contributing to Silver-Russell syndrome is presented.
• The review highlights the diagnostic value of extensive genetic testing strategies.
• Significant epigenetic and phenotypic similarities with other imprinting disorders are identified.

Conclusions:

• Accurate diagnosis of Silver-Russell syndrome requires thorough investigation of multiple genetic loci and tissues.
• Trio screening (proband and both parents) is crucial for identifying complex imprinting defects.
• Understanding overlaps with other imprinting disorders aids in differential diagnosis and management.