Deep Learning Detection of Retinitis Pigmentosa Inheritance Forms through Synthetic Data Expansion of a Rare Disease Dataset

Accurate classification of inheritance patterns is an integral part of diagnosis and genetic counseling for inherited retinal diseases (IRDs). Traditionally reliant on pedigree analysis, clinical phenotyping, and genetic testing, this process is often constrained by incomplete family history, ambiguous presentations, limited access to genetic testing, and inconclusive genetic test results. Deep learning (DL) applied to fundus imaging presents a promising approach for automated inference of inheritance modes; however, development has been hindered by the low prevalence of IRDs and the scarcity of annotated datasets. In this study, we focus on retinitis pigmentosa (RP), a highly heterogeneous disorder in both clinical presentation and genetic etiology. We present a first-in-class deep learning approach that leverages Vision Transformer (ViT) models to distinguish autosomal from X-linked RP using color fundus photography. To overcome challenges posed by limited data, we introduce an innovative variational autoencoder–based data expansion strategy, which improves inheritance pattern classification based on color fundus photos from 0.67 AUC to 0.79 AUC. Our findings demonstrate the potential of deep learning to uncover subtle phenotypic differences linked to genetic inheritance and introduce a novel training data augmentation method to render deep learning accessible to rare diseases.