A. All 4 core features of Silver-Russell syndrome (SRS) present and no cause found
B: 3 or more features present and family history of SRS or other imprinting disorder; or recurrent fetal loss with IUGR
C: 3 or more features present and multilocus imprinting defect
D: Isolated/single locus 11p15 methylation defect (H19 loss of methylation) with a family history of Silver-Russell syndrome.
Recruitment of relatives in these families should follow standard guidance.
E: Isolated/single locus 11p15 methylation defect (H19 loss of methylation) without a family history of Silver-Russell syndrome.
Recruitment to families in group E should occur only as proband-mother-father trios.
Core clinical features of Silver-Russell syndrome:
- Small for gestational age (birth weight and/or length <-2SDS) +- history of intrauterine growth retardation;
- Post-natal short stature (<-2 SDS )
- Body asymmetry
- Marked feeding difficulties in infancy / childhood +/- BMI 1.5 SDS relative to birth weight / length).
- Other known short stature syndrome
- Causative UPD (including UPD7, UPD14, UPD16, UPD20)
- Causative chromosome rearrangement
- Isolated methylation defect other than in familial cases
Prior genetic testing guidance
– Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
– Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.
PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.
Prior genetic testing genes
UPD7 testing and 11p15 methylation testing are required PRIOR TO RECRUITMENT as molecular diagnosis determines eligibility and methylation abnormalities cannot be detected on WGS.
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
Multi-locus methylation testing
These requirements will be kept under continual review during the main programme and may be subject to change.