From variants to answers: The evolution of genetic counseling in IEI

Inborn errors of immunity (IEIs) comprise >500 rare congenital disorders of the immune system, characterized by susceptibility to infection and immune dysregulation. Genetic testing advances have improved the comprehension of their molecular mechanisms and informed personalized therapeutic strategies. Nevertheless, the interpretation of variants and their clinical relevance remain challenging. Together with the technological limitations of next-generation sequencing and emerging methods, this highlights the need for standardized, reproducible approaches. The decision-making needs to incorporate effective genetic counseling, ethical and communicative considerations, and collaboration between clinicians, geneticists, and bioinformaticians. Ensuring equitable access to advanced genetic diagnostics is crucial to support accurate diagnoses, guide clinical management, and inform family planning. All this together highlights the need to combine clinical expertise and genetic research into an interdisciplinary collaboration, enabling individualized treatment and improved outcomes for individuals with IEIs.