Parents' understanding of genome and exome sequencing for pediatric health conditions: a systematic review

Genome and exome sequencing (GS/ES) offer significant advancements in diagnosing and treating pediatric health conditions. However, the complexity of GS/ES introduces psychosocial and ethical challenges, particularly regarding informed consent, privacy, confidentiality, and the interpretation of uncertain or secondary findings. Ayuso et al.'s framework provides key elements for informed consent to GS/ES. This study addresses the critical need to understand parental comprehension of GS/ES. Caregivers often overestimate the potential benefits of GS/ES due to low health and genomic literacy, and the emotional stress associated with a child's serious illness can further impede understanding. The study aims to summarize evidence on parents' actual and perceived understanding of GS/ES, and factors influencing this understanding, differentiating between verifiable "actual" and self-reported "perceived" understanding. Identifying gaps in understanding will inform improvements in consultations and informational resources.

The introduction cites several studies highlighting challenges in achieving informed consent for GS/ES, including the potential for overestimation of benefits and the impact of low health literacy and emotional distress. The authors emphasize the importance of both actual and perceived understanding in informed decision-making and information-seeking behaviors. Existing literature points to the challenges in parental understanding of complex genomic concepts and the need for improved communication strategies and resources.

The researchers conducted a systematic review following PRISMA guidelines. They searched four databases (Ovid MEDLINE, Embase, APA PsycINFO, and CINAHL) from 2008 to 2021, also searching Google Scholar and reference lists. Studies were included if they evaluated parental understanding of GS/ES in children with symptomatic health conditions, excluding prenatal or adult-onset conditions. Two reviewers independently screened abstracts and full texts, calculating Cohen's kappa for inter-rater reliability. The Mixed Methods Appraisal Tool (MMAT) assessed study quality. Data extraction included study design, measures of understanding, type of GS/ES, study context, and sociodemographic information. Data synthesis utilized Ayuso et al.'s framework, and heterogeneity precluded meta-analysis. The authors describe that they found 1264 unique articles initially, of which 16 studies fulfilled all inclusion criteria. They explain methods for deduplication and screening of abstracts and full-text articles. They detail the quality assessment process.

The review included 16 studies involving 1487 parents. Many parents had prior genetic testing experience or genetics-related exposure. The studies used diverse methodologies (qualitative, quantitative, and mixed methods) to assess understanding. **Parent Actual Understanding:** Parents demonstrated good understanding of GS/ES' potential to provide a more comprehensive diagnosis and improved clinical management compared to other genetic tests, and of its potential psychological benefits (e.g., relief of guilt, peace of mind). However, understanding was weaker regarding the scope of GS/ES, the distinction between different types of genetic tests, the depth of DNA analysis, the probability of obtaining secondary findings, and data privacy and confidentiality. There was some mis-understanding about de novo vs. inherited variants, and the implications of *not* finding a causative genetic variant. There were inconsistencies in parental understanding around the nature of secondary findings, including what conditions could be associated with secondary findings and whether parents would be informed about all secondary findings or only clinically actionable ones. Some parents misunderstood that a lack of a causative variant does not eliminate the possibility of a genetic cause or the risk to siblings. **Parent Perceived Understanding:** Results on perceived understanding were mixed. Studies reported varying levels of parental confidence in their understanding, with greater confidence in understanding voluntary participation and benefits of testing but less confidence in understanding potential discrimination and implications of secondary findings. One study showed a positive correlation between baseline actual understanding and perceived understanding after receiving results. **Factors Associated with Understanding:** Higher education levels, genetic understanding, health literacy, higher income, English proficiency, non-Hispanic white ethnicity, and greater cultural acculturation were associated with stronger actual understanding. Genetic counseling consultations significantly improved understanding.

The findings demonstrate variability in parental understanding of GS/ES, highlighting the need for improved communication and support for healthcare professionals. While parents generally understood the potential benefits, comprehension of risks, particularly regarding secondary findings and data usage, was less robust. The study's findings support the need for thorough pre-test counseling, tailored to individual family needs and literacy levels, emphasizing potential limitations as well as benefits. The emotional intensity of the situation should be acknowledged and addressed during the informed consent process. The significant improvement in understanding associated with genetic counseling underscores the value of providing such consultations.

Parents appreciate GS/ES' potential benefits, but understanding of risks related to secondary findings and data usage needs improvement. Variability in perceived understanding is also evident. Healthcare professionals should strive to thoroughly assess parental understanding, tailor information accordingly, and provide ongoing support. Future research should use validated measures to comprehensively assess both actual and perceived understanding, explore the impact of different counseling interventions, and investigate the relationship between understanding, satisfaction, and psychosocial factors.

The review's limitations include the focus on English-language studies, the exclusion of certain conditions, the heterogeneity of study methodologies, and the limited data on perceived understanding. The variability in study contexts and the different stages at which understanding was assessed also limit direct comparison of findings. The authors did not control for differences in counseling provided or access to resources.