A timely review in Journal of Paediatrics and Child Health highlighted the recent introduction of chromosomal microarray (CMA) for the evaluation of patients with unexplained intellectual disability and/or congenital malformations. The introduction of CMA is part of a broader trend in genetic testing, away from targeted testing and towards high-resolution, genome-wide testing. While genome-wide testing offers considerable advantages in terms of improved sensitivity and, ultimately, decreased cost, it also brings two specific challenges that warrant attention.
The first of these challenges is a laboratory result of ‘uncertain significance’. With CMA and other genome-wide testing, results of uncertain significance are generated at a much higher frequency than with traditional genetic tests. Therefore, there is a need to understand the potential impact of reporting these findings back to patients and their families.
The only example to date of research describing how families understand CMA results reports a number of factors that may contribute to difficulties in comprehending uncertain results. The authors make recommendations to improve the process of understanding CMA results, such as the development of written materials to be used for pretest counselling and production of resources to put families in touch with support groups and to access reliable information. The formation of these recommendations highlights the value of research into this area and further investigation is needed to inform and strengthen the authors' suggestions.
The second challenge resulting from genome-wide testing is the incidental finding. While incidental findings were previously rare in genetic testing, due to the fact that most genetic testing has been targeted to a specific gene, incidental findings are significantly more common with high-resolution, genome-wide testing technologies. A recent study by Green et al. shows that there is no consensus among genetic specialists in terms of returning some types of incidental findings from whole-genome sequencing in a clinical situation. This discordance was even greater when evaluating the return of paediatric patients' results. Research is needed to explore how specialists' opinions compare to patient preferences.
With the increasing clinical use of genome-wide, high-resolution genetic tests such as CMA and whole-genome sequencing, dilemmas about disclosing uncertain results and incidental findings will be encountered frequently. We are unprepared for this challenge. There is an immediate need for more research into the impact of providing patients with results of uncertain significance and disclosing incidental findings.