3D phenotyping in a Colombian population reveals unique population and ontogenic facial patterns in genetic and rare disorders

BackgroundApproximately 30-40% of genetic and rare disorders manifest with distinct facial patterns. Traditionally, clinical geneticists have qualitatively assessed facial morphology to support preliminary diagnosis and guide confirmatory genetic testing. However, enhancing early diagnostic accuracy through facial biomarkers demands advanced 3D technologies for analyzing facial dysmorphologies, a deeper understanding of condition-specific disruptions in facial development, and a broader inclusion of diverse human populations. To bridge this gap, we analyzed the 3D phenotypes associated with four genetic syndromes in an admixed Latin American population from Colombia. The sample comprised 47 individuals diagnosed with Down (DS), Morquio (MS), Noonan (NS), and Neurofibromatosis type 1 (NF1) syndromes along with 49 controls within the same age range. For each participant, we generated a 3D facial model using a multi-camera photogrammetric system and registered the 3D coordinates of 21 anatomical facial landmarks. Geometric morphometrics methods were employed to characterize syndrome-specific 3D facial dysmorphologies and to assess their variation compared to controls. We also examined whether these syndromes alter the ontogenetic trajectory of facial growth. ResultsFacial shape differed significantly in all syndromes except NF1. Consistently with previous 2D studies, we identified population-specific facial features in Colombian patients that are not reported in individuals of European descent. Pooled 3D analyses revealed a continuous spectrum of facial dysmorphology, with MS displaying the most distinct morphology and an altered ontogenic pattern. Facial size, sex and age were all significant factors modulating facial shape, with diagnosis explaining 14% of variation in facial morphology. ConclusionsOverall, these findings highlight the importance of accounting for interpopulation, sex and ontogenic variation in facial phenotypes to improve the diagnostic utility and of facial biomarkers. Such approaches may contribute to shortening the diagnostic odyssey for individuals with syndromic and rare genetic conditions.