- Coarse facial features warranting further investigation particularly those with other medical problems, additional dysmorphic facial features or intellectual disability, AND
- Previous investigations to exclude metabolic disorder including a minimum of plasma amino acids, urine organic acids and urine GAGs,
- Known genetic aetiology
- Untreated congenital hypothyroidism
- Metabolic investigations indicative of likely inborn error of metabolism (these individuals should follow a metabolic pathway of investigation and recruitment)
- Clinical features of an insulin resistance / lipodystrophy disorder, RASopathy or overgrowth disorder (these individuals should be investigated and recruited to the relevant specific rare disorder)
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
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
- Guided by phenotype. There should be a low threshold for Ras-MAPK gene testing, and 11p15 methylation analysis should be considered
- If clinical diagnosis of Pallister-Killian syndrome is considered likely, a skin biopsy for chromosome analysis should be performed prior to recruitment
These requirements will be kept under continual review during the main programme and may be subject to change.« Back to Disease List