Congenital Hyperinsulinism in the Era of Precision Medicine: Genetically Driven Diagnosis and Novel Therapies

Background/Objectives: Congenital hyperinsulinism (CHI) is the leading cause of persistent hypoglycaemia in infancy and childhood characterized by dysregulated insulin secretion despite low plasma glucose concentrations. Early recognition and treatment are essential to reduce the risk of neurological injury. Advances in molecular genetics have revealed substantial genetic and phenotypic heterogeneity beyond classical KATP-channel disorders. This review examines the expanding genetic landscape of CHI and the translation of molecular discoveries into precision clinical care.

Methods

This narrative review, based on targeted literature searches of PubMed/MEDLINE, Scopus and Embase and expert selection of key publications, synthesizes current evidence on the genetic mechanisms, genotype–phenotype relationships, molecular diagnosis, and clinical management of CHI, with emphasis on established and emerging genetic subtypes and their implications for therapeutic decision-making.