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).