RESUMEN
The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.
RESUMEN
Positive family history is known to be an independent risk factor for venous thromboembolic (VTE) that may or may not reflect an underlying hereditary disorder. However, there is no clear standardized definition of what constitutes a positive family history for VTE in children. We aimed to assess the current published definitions of positive family history as a risk factor for VTE in children and ascertain if any consensus exists. METHODS: We conducted a literature review through two major databases PUBMED and EMBASE (1969-June 2018). Three different search statements were used for each database to maximize the number of relevant results, giving rise to 1050 non-duplicated papers. RESULTS: Of the 1050 papers, 32 articles demonstrated 18 separate definitions on what constitutes a positive family history in paediatric studies. Variations in definitions were related to the closeness of kinship (first or second-degree relatives), whether thrombosis was provoked or unprovoked, the age of presentation of thrombosis in the kinship, and clinical vs. laboratory definition of positive family history. Of the definitions, 1st degree relative/s developing VTE at any age whether provoked or unprovoked was most commonly described. CONCLUSION: According to this literature review, the definition of a positive family history in paediatric populations is non-standardized amongst current published papers. To enable accurate comparisons across studies and improve clinical risk assessment, we therefore propose the need for a standardized definition of what constitutes a positive family history.
