Patients' reactions and follow‐up testing decisions related to Tay‐Sachs (HEXA) variants of uncertain significance results

Abstract

JScreen is a national public health initiative based out of Emory University that provides reproductive carrier screening through an online portal and follow‐up genetic counseling services. In 2014, JScreen began reporting to patients variants of uncertain significance (VUSs) in the gene that causes Tay‐Sachs disease (HEXA). Genetic counseling was provided to discuss the VUS and patients were offered hexosaminidase A (HEXA) blood enzyme testing to assist with VUS reclassification. To identify patient reactions and factors influencing their follow‐up testing decisions after receiving these results, we conducted a retrospective quantitative study by administering online surveys to 62 patients with HEXA VUSs. Participants who pursued enzyme testing and those who did not both experienced low levels of distress when receiving the VUS results. Perceptions of HEXA carrier status after genetic counseling, decisional conflict levels, plans to have children in the near future, time available to pursue enzyme testing, and eligibility for research were significant factors influencing decision‐making to pursue or not pursue enzyme testing. Genetic counseling played an important role in helping patients understand the VUS and follow‐up testing options. When discussing VUSs with patients, it would be beneficial for genetic counselors to focus on the patient's perception of the VUS, anxiety related to the uncertainty of their results, and follow‐up options, when available.

Systematic review of outcomes in studies of reproductive genetic carrier screening: Towards development of a core outcome set

“…A single time point was assessed by most studies (n = 41, 85%) and included audit data from databases between 1-30 years since screening (n = 34, 83%), 29,30,[32][33][34][35][36]38,40,42,[47][48][49]52,57,60,61,[63][64][65][67][68][69]73,74,78,81,[83][84][85][86][87][88]90,91,93 patient-reported outcomes at pre-test counselling after the decision to accept or decline was made (n = 3, 7%), 75,76,82 after maternal results but before partner results (n = 1, 2%), 39 and after results between 1-2 years since screening (n = 3, 7%). 46,51,53,55,56,58,59,66,92 Seven stud...…”

“…There is enough evidence that psychological harm caused by the offer and/or participation is negligible CODECS outcome domains of 'psychological wellbeing' and 'perception of personal health status after RGCS' were mapped to this criterion. Psychological wellbeing was reported in 20% (n = 9) of studies, 43,44,54,56,62,71,72,76,89,92 and perceptions of personal health status was reported in a single study. 71 There is enough evidence that social harm caused by the offer and/or participation is negligible CODECS outcome domains of 'affected births', 'reproductive decision-making', 'non-reproductive decisionmaking', 'familial implications', and 'privacy concerns and stigmatisation' were mapped to this criterion.…”

“…29,30,32,35,38,40,48,58,60,64,67,69,73,84,86 The outcome domain of 'reproductive decision-making' was reported in 10% (n = 5) studies. 46,58,59,62,70,71,76,92 Assessment of social impact or harms outside of reproductive decisions and birth rates was limited to a handful of studies and included assessing the impact of results on the couple's relationship, dissemination of results to family members, concerns regarding discrimination by insurance companies, and fear of stigmatisation within the community. 52,54,62,71,89 See Box 1 for a quick summary of the findings.…”

“…The outcome domain of 'psychological wellbeing' was reported in 20% of studies. 43,44,54,56,62,71,72,76,89,92 Ten different outcomes were used to measure psychological wellbeing; anxiety, concern, depression, feelings about results, perceived ability to cope, predicted negative feelings, reassurance, stress, subjective distress, and worry. Of these, the most frequently reported was anxiety.…”