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GENATLAS PHENOTYPE
last update : 28-09-2011
Symbol SRS11
Location 11p15.5
Name Silver-Russell syndrome, chromosome 11 related
Corresponding gene H19 , IGF2
Other symbol(s) SRS, RSS, DUP11P15
Main clinical features
  • severe intrauterine and postnatal growth retardation (<3rd percentile) with preservation of OFC, feeding difficulties
  • dysmorphic facial features : triangular facies, pointed chin
  • body asymmetry with hemihypotrophy, and clinodactyly Vth
  • Genetic determination epigenetic
    Related entries SRS7, UPD7M, SRS17, SRSX
    Function/system disorder multisystem/generalized
    mental retardation
    Type MCA/MR
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    imprinting defect     methylation defect of the 11p15 telomeric domain imprinting center, ICR1, usually hypomethylation at both the H19 and IGF2 genes, but hypomethylation may be restricted to either the H19 or the IGF2 gene.
      duplication   maternal duplication of 11p15
      uniparental disomy   mosaic UPD mat in 1 case
    imprinting defect     multilocus LOM
      duplication   microduplication restricted to the ICR2 domain results in SRS when maternally transmitted PMID: 21910219
    Remark(s)
  • up to 50 percent of SRS cases are associated with detectable disturbances in 11p15, opposite mutations are associated with BWS; epimutations in siblings of normal parents, most likely reflecting germ cell mosaicism in the fathers (Bartholdi,09)
  • paternal ICR1 loss of methylation in 60p100 of SRS cases (Demars 2010)
  • Genotype/Phenotype correlations patients carrying epimutations had a more severe phenotype than either the SRS patients with mUPD7 or the idiopathic SRS patients; phenotype severity is correlated with degree of H19 methylation, with specific association of skeletal and genital defects in severe hypomethylation (Bruce,09)