By Barbara Greenwood Dufour
For many children who aren’t meeting expected developmental milestones, the cause isn’t easily found. Without other observable signs or symptoms or known external factors that could explain the developmental delay, these children undergo multiple diagnostic tests in an effort to get a diagnosis. Unfortunately, in many cases the tests don’t reveal a cause.
For families of children with unexplained developmental delays, it can be disheartening to have spent years on a “diagnostic odyssey” only to be told that no reason for their child’s condition can be found. If the condition has a genetic basis, however, genetic sequencing might be able to uncover the cause where traditional testing could not.
Although genetic sequencing was introduced into health care in the 1970s, recent developments in the biotechnology sector have made genome-wide sequencing faster and less expensive. These next-generation, or high-throughput, sequencing technologies require patients to undergo a standard blood draw that is sent off to a lab. Highly specialized professionals then sequence, analyze, and interpret the results to determine if there are genomic variations that could be responsible for the developmental delay.
Genome-wide sequencing isn’t broadly available in clinics in Canada and is, instead, conducted only as part of research studies primarily at academic centres. Yet, many Canadian parents of children experiencing developmental delays have become interested in this technology. If genome-wide sequencing were to be made broadly available, what might parents expect to experience? What supports might they need as they navigate a new odyssey after having found a genetic explanation for their child’s condition?
To find out, CADTH — an independent agency that finds, assesses, and summarizes the research on drugs, medical devices, tests, and procedures — conducted a review of the available qualitative studies that described the experiences of families that had accessed genome-wide sequencing to understand the reason for their child’s unexplained developmental delay. After screening the literature, CADTH reported on 13 studies, which captured the experiences using interviews, video-recorded consultations, and questionnaires.
According to the studies, most parents whose children received a diagnosis of a genetic disorder reported feeling relieved that their diagnostic odyssey was over. However, the need to know and understand the cause of their child’s condition is rarely the sole goal of families undergoing genetic testing. They also hope that the newly identified cause will open the door to new or different treatment options. But, for most parents, this isn’t the case.
Despite having received no more than a name and an explanation for their child’s condition — that is, the test results were not “clinically actionable” — some parents in the studies seemed able to adopt a positive outlook. They reported being hopeful that future research would soon provide a better understanding of their child’s condition, resulting in new treatments becoming available. Others indicated that they had been able to change their focus from treatment to helping their children reach their potential, gaining a sense of renewed purpose as a result.
But other families were left frustrated about the lack of clinical actionability. Many of them had expected that once the genetic disorder had been diagnosed there would be a treatment for it. They were unprepared to find out that, as is the case for many genetic disorders, there are no treatments available. Some parents also reported being unprepared to deal with other consequences — for example, the sense that the burden of care, previously shared with the health care professionals investigating their child’s condition, was permanently and solely on them; the concern that other family members, such as siblings of the child, might have the same genetic mutation(s); and a sense of guilt about having passed the mutation(s) to their child.
The fact that many families are unprepared to deal with certain consequences of a genetic diagnosis suggests that clinical geneticists and genetic counsellors could play a role in alleviating their negative feelings. One of the studies — which observed consultations families had with a clinical geneticist and genetic counselor on issues such as disability care, reproductive decision-making, and emotional management — reported that parents found these consultations valuable.
CADTH’s review suggests that whether genome-wide sequencing leaves families with a positive or a negative outlook might be influenced by the quality and content of the conversations they have with clinicians beforehand. If access to this technology for the diagnosis of children with unexplained developmental disabilities were to be expanded to clinics in Canada, genetic counselling would likely help prepare families for the potential outcomes and implications, similar to the current practice of providing genetic counselling for all genetic testing.
The full qualitative review is freely available on our website. If you’re interested in this topic, you might also be interested in an upcoming Health Technology Assessment project that CADTH is conducting, in collaboration with Health Quality Ontario, on the use of genome-wide sequencing for patients with unexplained developmental disabilities and multiple congenital anomalies.
Barbara Greenwood Dufour is a Knowledge Mobilization Officer at CADTH.