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Russell–Silver syndrome
Author(s) -
Eggermann Thomas
Publication year - 2010
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.30274
Subject(s) - epigenetics , genomic imprinting , biology , uniparental disomy , genetics , phenotype , dna methylation , angelman syndrome , chromosome 7 (human) , imprinting (psychology) , karyotype , chromosome , methylation , chromosomal rearrangement , bioinformatics , gene , gene expression
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.