Testing whole genome sequencing in the paediatric clinic

Appropriately implementing novel technologies involves critically considering how and when to use them. The technology of next-generation DNA sequencing and its application in whole genome sequencing (WGS) is a key example of where this 'how and when' problem arises. Genomics challenges presumptions, such as whether possible applications of a technology should lead its implementation, or whether it should instead be guided by a core clinical question. And when the individual being tested is a child, these considerations become more significant.

While the idea of using a particular test to help obtain a diagnosis is certainly not new, some features of WGS arguably set it apart from more ‘traditional’ clinical genetics.1 It can give rise to significant volumes of information. Not all of this is yet understood, some has been previously overinterpreted and its meaning will almost certainly change with time.2 WGS will not always lead to certainty, and may introduce new uncertainties.3

This is not to say that WGS is inherently problematic. It has huge potential to positively impact clinical practice, mitigating the effects of illness and improving quality of life for children and their families. We are already seeing families benefiting from obtaining a diagnosis following genomic testing.4 But at the same time, we should be mindful not to bestow more to genomics than it is capable of providing.

Anderson et al5 evaluated one such implementation of paediatric clinical WGS, the Genome Clinic study. The study involved WGS in children with an underlying condition to identify: (i) primary variants to explain the child's clinical presentation, (ii) other medically actionable variants for conditions that present in childhood; (iii) pharmacogenetic variants relevant to the child's illness and (iv) medically actionable variants for conditions that typically present in adulthood (secondary variants (SVs)). Parents considering their child's potential …