Silver-Russell syndrome

The Silver-Russell syndrome (SRS) is a sporadic clinically and genetically heterogeneous disorder. Diagnosis is based on the variable combination of the following characteristics: intrauterine growth retardation, short stature because of lack of catch-up growth, underweight, relative macrocephaly, typical triangular face, body asymmetry and several minor anomalies including clinodactyly V. Different diagnostic scores have been proposed. The main genetic defects detected are at the epigenetic level: hypomethylation of the imprinting control region 1 (ICR1) on 11p15 in around 44% of cases and maternal uniparental disomy of chromosome 7 (UPD(7)mat) in 5-10% of cases. Severe phenotype is frequently associated with hypomethylation of ICR1 while mild phenotype is more often seen in combination with UPD(7)mat. Origins and biological consequences of these epimutations are still obscure. For genetic testing, we recommend a methylation-specific PCR-approach for both 7p and 7q loci (confirmed by microsatellite typing) for the detection of UPD(7)mat, and the methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) approach for methylation analysis of the 11p15 loci. Short stature in SRS can be treated by use of pharmacological doses of recombinant GH resulting in good short-term catch-up; sufficient information on the therapeutic effect in terms of final height is still missing.