Quantitative Facial Phenotyping and Age-Associated Differences in Sickle Cell Disease Using Interpretable Machine Learning
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Background Sickle cell disease (SCD) is a common inherited genetic disorder and contributor to global childhood mortality and morbidity, particularly in Sub-Saharan Africa. Craniofacial and skeletal changes have been described in SCD, but the subtle soft-tissue facial patterns and their variation have not been quantitatively characterized using machine-learning methods. Methods We analyzed 308 front-facing smartphone photographs from 154 participants with electrophoresis-confirmed SCD and 154 age- and sex-matched controls aged from 5 months to 19 years recruited in Kinshasa, Democratic Republic of the Congo. Predefined geometric and texture-based facial descriptors were extracted from standardized images using manually annotated landmarks. An interpretable linear support vector machine with recursive feature elimination was evaluated using leave-one-out cross-validation, with features ranked according to their relevance for distinguishing participants with SCD from controls. Cross-sectional age- and sex-stratified analyses evaluated variation in selected features Results The facial analysis algorithm identified eight geometric and six texture discriminative features that were significantly different between the cohorts. A combination of six geometric features contributed most consistently to internal discrimination: distance between medial and lateral canthi, angle at nasal ala, distance from nasion to philtrum, distance from medial canthi to the columella, distance from columella to the lower lip, and distance between nasal alae. The model achieved an AUROC of 0.843 [95% CI: 0.798,0.887], and an accuracy of 0.795 [95% CI: 0.750,0.840]. Between-group difference was limited in the youngest age groups and were more pronounced in several older age groups. Conclusion: These findings demonstrate preliminary evidence that SCD is associated with quantifiable morphometric patterns. External, longitudinal, and clinically characterized studies are needed to determine whether these features may serve as reproducible digital biomarkers within a broader supportive disease-assessment framework. Author Summary Sickle cell disease (SCD) is a genetic blood disorder that affects millions of people worldwide and is a major cause of illness and death in children, specifically in Sub-Saharan Africa. Previous studies have described changes in facial and craniofacial development among people with SCD but many of these changes require special assessment or medical imaging. We examined whether measurements obtained from standardized smartphone photographs could quantify facial differences associated with SCD. We collected 308 front-facing photos of children with SCD and matched healthy controls between 5 months and 19 years old. Using computer-based facial analysis, we measured a range of geometric and texture features and used interpretable machine-learning methods to determine which ones best distinguished children with SCD. The model identified a small set of geometric facial measurements that significantly differed between groups, with larger differences observed in several older age groups. The findings provide a basis for future longitudinal and externally validated studies of facial morphology as a potential digital biomarker of disease-associated change.
Source: medRxiv
Authors: D’Andre Spencer, Xinyang Liu, Kizito Mosema-Be-Amoti, Gisèle Kandosi, Matthew S Bramble, Faisal Al Munajjed, Esther Likuba, Daniel Okitundu-Luwa E-Andjafono, Laure Tshibambe, Brian Colwell, Kristen Howell, Nicole O’Brien, Christopher Moxon, Syed Muhammad Anwar, Antonio R Porras, Dieudonne Mumba Ngoyi, Eric Vilain, Desire Tshala-Katumbay, Marius George Linguraru
Institutions: Children's National, University of California, Irvine, Sheikh Zayed Institute for Pediatric Surgical Innovation, National Institute of Biomedical Research, University of Kinshasa, Texas A&M University, Nationwide Children's Hospital, The Ohio State University, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Kamuzu University of Health Sciences, University of Glasgow, George Washington University, Colorado School of Public Health, University of Colorado Anschutz, Oregon Health & Science University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7134918368