ProtoGestalt: Interpretable Prototypes for Facial Phenotyping and Diagnosis of Rare Genetic Disorders

Abstract

Rare genetic disorders are difficult to diagnose due to their diversity and overlapping clinical features. Facial morphology can provide diagnostic clues, yet most diagnostic models offer limited interpretability and are not designed to support broad screening for undiagnosed disease. We present ProtoGestalt, an interpretable prototype-based framework for facial phenotyping, rare-disease screening, and syndrome identification. The method extends prototype learning by constraining learned visual features to select facial regions, allowing predictions to be explained through localized and additive evidence. We assess ProtoGestalt's ability to distinguish syndromic from unaffected faces on multiple control datasets and class prevalence values. We further evaluate it's diagnostic performance on syndromes observed during training. The learned prototype-based representations provide significant separation between syndromic and case-matched control images and retain useful performance as the proportion of controls increases. The framework also demonstrates the ability to differentiate among syndromes. Although reasonably accurate specialized models for facial classification of rare disorders already exist, ProtoGestalt offers an interpretable alternative that links predictions to anatomically meaningful facial regions, potentially supporting clinical decision-making and the discovery of phenotype-gene associations.