Artificial Intelligence in the Diagnosis of Pediatric Rare Diseases: From Real-World Data Toward a Personalized Medicine Approach.

Abstract

Background: Artificial intelligence (AI) is increasingly applied in the diagnosis of pediatric rare diseases, enhancing the speed, accuracy, and accessibility of genetic interpretation. These advances support the ongoing shift toward personalized medicine in clinical genetics. Objective: This review examines current applications of AI in pediatric rare disease diagnostics, with a particular focus on real-world data integration and implications for individualized care. Methods: A narrative review was conducted covering AI tools for variant prioritization, phenotype-genotype correlations, large language models (LLMs), and ethical considerations. The literature was identified through PubMed, Scopus, and Web of Science up to July 2025, with priority given to studies published in the last seven years. Results: AI platforms provide support for genomic interpretation, particularly within structured diagnostic workflows. Tools integrating Human Phenotype Ontology (HPO)-based inputs and LLMs facilitate phenotype matching and enable reverse phenotyping. The use of real-world data enhances the applicability of AI in complex and heterogeneous clinical scenarios. However, major challenges persist, including data standardization, model interpretability, workflow integration, and algorithmic bias. Conclusions: AI has the potential to advance earlier and more personalized diagnostics for children with rare diseases. Achieving this requires multidisciplinary collaboration and careful attention to clinical, technical, and ethical considerations.