Delivering genome sequencing for rapid genetic diagnosis in critically ill children: parent and professional views, experiences and challenges

Abstract

Rapid genomic sequencing (RGS) is increasingly being used in the care of critically ill children. Here we describe a qualitative study exploring parent and professional perspectives around the usefulness of this test, the potential for unintended harms and the challenges for delivering a wider clinical service. The Rapid Paediatric Sequencing (RaPS) study offered trio RGS for diagnosis of critically ill children with a likely monogenic disorder. Main and actionable secondary findings were reported. Semi-structured interviews were conducted with parents of children offered RGS (n = 11) and professionals (genetic clinicians, non-genetic clinicians, scientists and consenters) (n = 19) by telephone (parents n = 10/professionals n = 1) or face-to-face (parents n = 1/professionals n = 18). We found that participants held largely positive views about RGS, describing clinical and emotional benefits from the opportunity to obtain a rapid diagnosis. Parental stress surrounding their child’s illness complicates decision making. Parental concerns are heightened when offered RGS and while waiting for results. The importance of multidisciplinary team working to enable efficient delivery of a rapid service was emphasised. Our findings give insight into the perceived value of RGS for critically ill children. Careful pre-test counselling is needed to support informed parental decision making. Many parents would benefit from additional support while waiting for results. Education of mainstream clinicians is required to facilitate clinical implementation.

Genetic Testing in the Pediatric Nephrology Clinic: Understanding Families' Experiences

“…Our findings suggest that compassionate family–clinician partnerships were important to parents throughout the genetic testing process and contributed to easing emotional distress. 15 As reported in other studies, trusting clinical partnerships appeared to be associated with more positive experiences undergoing testing 16 and clinicians who tailored genetic information to fit the families' needs were highly valued. 17 Most parents reported experiencing anxiety while awaiting the test results and after receiving the results.…”

“…This was further reflected in our quantitative measures which indicated distress and uncertainty for their child's future were highest at the time of diagnosis following genetic testing. Undergoing genetic testing can be an additional stressor for parents caring for a child with chronic illness, 15 and both diagnostic and prognostic ambiguity can cause significant psychological distress and contribute to long-lasting emotional burden. 18,19 Our findings indicate that parents may benefit from genetic counseling to support understanding of the purpose, potential benefits, and limitations of genetic testing, as well as to provide additional support to manage expectations while waiting for the test outcomes.…”

“…18,19 Our findings indicate that parents may benefit from genetic counseling to support understanding of the purpose, potential benefits, and limitations of genetic testing, as well as to provide additional support to manage expectations while waiting for the test outcomes. 15,20 Given that parents valued information exchange between their pediatrician and the renal genetics team, developing clinical care plans which accommodate for the renal genetic team and the family pediatrician to be present when delivering genetic test results by use of videoconferencing tools that may offer benefit to both families and their clinicians.…”

Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)

“…Of note, parental stress surrounding their child's illness complicates their decision making and not unexpectedly their concerns are heightened when offered rGS and waiting for results. 81…”

A Formative Study of the Implementation of Whole Genome Sequencing in Northern Ireland

“…Many participants waited approximately three years for the return of results, a significant delay due to the logistical difficulties in delivering WGS and worsened by the COVID-19 pandemic. Analytical time is becoming shorter as improvements to genomic healthcare are implemented, with recent findings from the Newborn Sequencing in Genomic Medicine and Public Health study in the United States of America providing a diagnosis for infants from WGS in less than five days [ 29 ], and rapid genomic sequencing being offered to critically ill neonates in the UK through, for example, the Great Ormond Street Hospital for Children NHS Foundation Trust (GOSH), with other UK clinics now offering similar services [ 30 ].…”