Quantitative phenotypic data to confirm fit with diagnosis
Quantitative phenotype data and gene-specific centile charts:Quantitative phenotype data (developmental milestones or anthropometric measurements) can be recorded in DECIPHER, and are aggregated on a gene-by-gene basis and shared openly (Fig. 6A). In order for this information to be shown for a given gene there must be at least five patients with both quantitative phenotype data and openly shared sequence variants annotated as pathogenic/likely pathogenic. Once this threshold is met, DECIPHER automatically aggregates and shares the information as a series of graphs on which expectations for the predominantly healthy population (‘Normal’), the DECIPHER population as a whole, and the gene-specific data is plotted. Anthropometric measurements are plotted around the standard deviation (adjusted for sex and gestation, where possible), while developmental milestones are plotted against time. The standard deviation for each population is displayed at the bottom of the graph as a boxplot. For users logged into DECIPHER and looking at a patient record from their centre, a vertical line indicates their patient’s measurement or age at attainment of the milestone, allowing them to easily judge whether it is consistent with a pathogenic/likely pathogenic variant in the gene. The display of the DECIPHER population allows users to determine if a particular measurement is particularly discriminative for a given disorder. These gene-specific centile charts can also be used in the clinic to determine how a child is developing relative to other children with the same disorder.
Composite facial images: For certain genes there also are composite faces, which highlight facial dysmorphologies specific to a gene. These anonymised composite face images have been created from individuals with de novo mutations in the affected genes that were collected through the DDD study (Deciphering Developmental Disorders, Study, 2017).