We investigated parental understanding of CMA test results for children who were diagnosed with either a pathogenic alteration or a VUS. Three domains of understanding were identified: (i) comprehension of results, (ii) interpretations of scientific uncertainty, and (iii) personal meanings for the child and family. Receiving results by telephone, long waits to see a geneticist to discuss results, inconsistent information provided by different professionals, and Internet searches based on inadequate and/or inaccurate information all contributed to difficulties in comprehending results. We suggest that these can be addressed to reduce uncertainty and improve parents’ understanding of test results.
Some respondents preferred to receive results in person because a personal encounter allowed more in-depth discussion, the presence of multiple practitioners and family members, and the availability of visual materials. This is consistent with research in other medical genetics settings demonstrating increased satisfaction when patients have an option of receiving results by telephone or in person.25,26
Comprehension was also improved by discussing results with health providers (geneticists, genetic counselors, trusted non–genetics professionals, and a multispecialist team) and with medically informed relatives, friends, or support groups. Many of these practical issues are addressed in the Recommendations section below.
Consistent with a study by Makela et al
on parental responses to CMA testing for intellectual disability, we found that Internet searches had limited value and sometimes increased confusion. Rare CMA results may consist only of a chromosomal address or location of a deletion/duplication, rather than the name of a syndrome. Often, parents were aware only of the number of the chromosome with the deletion/ duplication, rather than the exact chromosomal address, breakpoints, and size. When searching the Internet without sufficiently detailed information, there is a tendency to find information about extremely severe conditions (e.g., very large deletions or insertions) that increases confusion and anxiety. Although some parents were warned by providers not to search online, many conducted searches anyway. There is a need for health professionals to explain specific details about the result, warn parents about the likelihood of finding inapplicable information on the Internet, and direct them to appropriate websites. Although many searches using the detailed test results may not be fruitful, this would at least avoid the needless distress that occurs when finding disturbing information that is not relevant. By reducing the negative outcomes associated with Internet searches, the Internet may become a valuable resource for information and/or support, as reported in several other studies.17,27–29
Recipients of results in both the VUS and the pathogenic categories expressed similar views regarding understanding the scientific uncertainties pertaining to the test results. This was somewhat surprising in light of research suggesting that parents of undiagnosed children and individuals with inconclusive results, as opposed to those with a definite diagnosis, experience greater stress and additional challenges in understanding results of genetic testing.16,17,19,30–33
However, for both categories of CMA results, there are often similar uncertainties regarding prognosis. Many pathogenic findings involve rare and newly identified genomic disorders.34
Parents of children with rare disorders are known to have high levels of perceived uncertainty due to limited prognostic information and variability of the clinical phenotypes.8,13
The line between some of the VUS results and the novel pathogenic results is not always clear, and some VUS results may, after more scientific investigation, become defined as novel syndromes. This may also explain why some parents in the VUS group reported finding a causal explanation for their child’s condition.
Although there are some similarities between the VUS and pathogenic groups in understanding of results, research has found that having an inconclusive, rather than a pathogenic, result can lead to different psychological and emotional responses, such as allowing for hope to be maintained.11–13,15,17
It is important for future research to identify aspects of genetic variations that may lead to differing emotional responses.The reshaping of identity in response to genetic information has been discussed in research regarding presymptomatic and diagnostic genetic testing.16,35,36
In the context of CMA testing, finding a genetic anomaly in parents may alter their self-concept if they discover that they carry the same copy number variation as other individuals who exhibit pathological features. Although beyond the scope of this article, it is important to consider the occurrence of incidental findings in the patient and other relatives tested. These types of unintended consequences will no doubt become more common as genome-wide testing becomes more widely available.32
Future research should address the ethical and psychosocial implications of CMA testing for asymptomatic relatives of patients tested, with respect to risk for disease, reproductive decisions, self-concept, and discrimination.
An important contribution of this study is the approach to clarifying different types of uncertainties and identifying those that can and cannot be reduced. Comprehension of test results can be improved by reducing uncertainties attributed to limitations in providers’ and family members’ personal knowledge of genetics, and improving the quality of communication about the results. Although the uncertainties stemming from limitations in scientific knowledge can only be resolved by future discoveries, it may be valuable for families to differentiate between different types of scientific uncertainties: for example, some pathogenic results provide a causal explanation but unclear prognosis because of the rarity of the finding; the implications of some VUS results may be unclear now, but future research may shed light on the impact of the copy number variation on the child’s health and development. When uncertainties are differentiated, families’ specific informational needs can be addressed more effectively. Scientific uncertainties that cannot be reduced at present may be addressed first by acknowledging them clearly and then by keeping abreast of relevant medical advances through appropriate follow-up with health providers and by participation in research studies, when available.
Increased understanding and knowledge may facilitate coping for parents of a child with a rare genetic disorder,6,29
and health providers have an important role in fostering skills that may help parents adapt and cope with the uncertainty and stress of their child’s condition.13,37
Our findings suggest that health professionals can help families to interpret and find meaning in their results by clarifying uncertainties that can be reduced and providing tailored information to address individual needs. Involving primary-care practitioners can be an effective means of providing care to children with special health-care needs.38
This highlights the need for continuing genetic education for primary-care physicians so that they can provide care and guidance for families undergoing CMA testing.39
Based on our findings, we make the following recommendations so as to improve the understanding process for families of children having CMA testing:
- Results should be provided by professionals with appropriate genetics expertise to accurately interpret and explain results, as articulated in recent professional guidelines.40
- Pre-test education and counseling is needed, and written materials need to be developed, to prepare families for potential diagnostic and prognostic uncertainties.
- Families should be provided with options for the mode of result delivery, either by telephone or in person.
- Post-test genetic counseling should be available soon after results are delivered, to address the medical and psychosocial implications of CMA results for the child and other family members, and inform families of how to keep abreast of new relevant scientific information.
- Resources need to be developed to enable parents to access reliable information and connect with other families with the same CMA finding.
- Guidance should be provided to families using Internet searches, in order to avoid finding misleading information.
- Genetics training for non–genetics specialists and primary health-care providers can help them to provide appropriate support for families and address the medical and psychosocial implications of test results.
There are several limitations to this study. First, we used a small convenience sample and generalizability is constrained. As our intention was to explore understanding of uncertain and abnormal results in the novel context of CMA testing, we excluded families with negative results. This allowed us to maximize our potential to investigate the impact of the results, but the sample is not representative of all families having CMA testing. Second, the different methods of recruitment yielded different response rates, and more fathers were recruited for in-person interviews than telephone interviews. Third, in this retrospective study, recollections of receiving results may be subject to recall bias. Fourth, the children tested varied in age and had a wide range of medical conditions, both of which are likely to influence understandings of the test results. It is important for future research to investigate understandings of CMA results among families with negative test results, specific phenotypes and genotypes, and different sociodemographic backgrounds.