Lekárska genetika a diagnostika 2/2026

The undiagnosed patients in the era of genomic medicine: from diagnostic odysey to a continuous diagnostic pathway

What happens to a patient when, even after years of investigation and the use of available genomic methods, the cause of their disease remains unknown? A negative result of genomic methods should not mark the end of the diagnostic journey or result in the patient being lost from the healthcare system. Undiagnosed patients need a clearly defined diagnostic status and an opportunity for systematic reassessment of their case. Such an approach requires unambiguous patient identification, rational use of genomic testing, standardized phenotypic and genotypic description, multidisciplinary assessment, reanalysis of existing data, and access to national and international expertise. An interoperable infrastructure enabling the secure storage, reuse and, under appropriate conditions, sharing of clinical and genomic data also plays an important role. For patients in whom appropriate routine diagnostic options have been exhausted, a pathway to research-based diagnostics should also be available, supported by sustainable national funding mechanisms and international collaboration.

Keywords: undiagnosed patient, rare diseases, genomic medicine, WGS, OPRHA codes, European Reference Networks