For clinicians it is a challenge to face a patient with a possible genetic disease. As knowledge about clinical genetics continues to expand, making the right interpretation of genetic variants is ever more complex. The types of genetic findings or variants they may encounter ranges widely, from a variant in a gene that manifests itself with different phenotypes within the same family or a monogenic variant showing different degrees of severity or even a set of variants contributing to a complex phenotype.
The suspicion of genetic disease is usually the consequence of recognising specific clinical features in a patient. These features may then be analysed as part of more complex phenotypes. Those phenotypes that are more specific because they appear only in certain syndromes or diseases, become ‘marker traits’ as their distinctiveness allow the identification of a more targeted group of pathologies.
The identification of more targeted phenotypes allows clinicians to ask whether the suspected disease is monogenic or whether it can be at least studied with a panel of genes. Many times there will be patients with conditions in which a specific alteration causing the pathological phenotype is not found, even when having enough evidence for genetic aetiology being the most likely case of the disease. In cases where a causative genetic marker for a suspected genetic aetiology is not found, this ends up being assumed a limitation of the available test.
Unfortunately, for those cases with a suspected genetic aetiology where the causal marker is not found, the patient and their families may end up in a ‘diagnostic odyssey’, having to endure many genetic tests throughout years, sometimes with no conclusive results.