Relevant diseases: –
- Classical Beckwith-Wiedemann syndrome
- Atypical Beckwith-Wiedemann syndrome
Clinical diagnosis of BWS meeting standard clinical diagnostic criteria EXCEPT THOSE WITH UPD 11p15, UNBALANCED TRANSLOCATIONS OR OTHER 11p15 COPY NUMBER DEFECTS OR CDKN1C MUTATIONS
Eligible patients will include those with
- No detectable cause
- Balanced chromosomal aberration (translocation/inversion)
- Multilocus methylation defect consistent with an in trans imprinting defect
- Isolated/single locus 11p15 methylation defect
Recruitment of families with Isolated/single locus methylation defects without a family history or BWS or other imprinted disorder should only occur as proband-mother-father trios.
- UPD 11p15
- Unbalanced translocations or other 11p15 copy number defects
- CDKN1C mutations
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
11p15 methylation testing is required PRIOR TO RECRUITMENT as molecular diagnosis determines eligibility and surveillance, 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:
These requirements will be kept under continual review during the main programme and may be subject to change.