Abstract
BACKGROUND: Although genomic testing is increasingly standard of care for diagnosing children and adults with genetic conditions, over 50% of genomic testing will return an uninformative result. AIM: To provide a practical guide for paediatricians on how to approach an uninformative genomic test result, and the pathways which may be available to uncover a genetic diagnosis for their patients. METHODS: Input from multiple genetics healthcare professionals including genetic counsellors, the literature, and a general paediatrician were used to construct this guide. We also provide a hypothetical case vignette, to further demonstrate the various options for a patient after receiving an uninformative result. RESULTS: There are several reasons why an underlying genetic diagnosis may not be diagnosed with current testing, including incomplete phenotyping, a different underlying genetic mechanism requiring specialised testing, and limitations in knowledge at the time of the test. CONCLUSION: Uninformative results are very common, and it is important to understand these results in the context of the limitations of genomic testing. General paediatricians play an important role in supporting families through their diagnostic odyssey, as well as reassessing the phenotype, referring for sub-specialty inputs, and discussion with local genetics services for consideration of alternative testing options or enrolment into research pathways.