Russell–Silver syndrome

AbstractIn 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 dif