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

The paper addresses how well parents of pediatric patients offered genome or exome sequencing (GS/ES) understand related concepts, distinguishing between actual (verifiable) and perceived (self-reported) understanding. GS/ES offers advances in diagnosis and treatment for pediatric conditions but raises psychosocial and ethical challenges around informed consent, privacy, limitations, variants of uncertain significance, and secondary findings. Prior literature indicates parents may overestimate the promise of GS/ES, with health/genomic literacy and emotional distress potentially impeding comprehension. In research-clinical hybrid contexts, therapeutic misconception can occur. Using Ayuso et al.’s framework for informed consent, the review aims to summarize evidence on: parents’ actual understanding, perceived understanding, and factors associated with understanding of GS/ES when testing is offered for a symptomatic child.

Background literature highlights the complexity of GS/ES informed consent and challenges for clinicians and genetic counselors. Parents can overestimate benefits of new genomic technologies; low health/genomic literacy and heightened emotions may hinder comprehension. In research settings, goals of understanding acquisition can be conflated with therapeutic expectations. The review adopts distinctions from prior work between actual and perceived understanding, both important for informed decision-making and information-seeking behavior. Ayuso et al.’s key elements for GS/ES informed consent guide organization of findings. Existing studies suggest variability in understanding of heredity versus more abstract topics (e.g., insurance risks, secondary findings), and that counseling may improve knowledge.

Systematic review conducted per PRISMA guidelines. Databases searched: Ovid MEDLINE, Embase, APA PsycINFO, and CINAHL. Initial search June 19, 2020, with a rerun March 18, 2021; supplementary searches via Google Scholar, citation tracking, and reference lists. Inclusion: English-language peer-reviewed studies (Jan 2008–Mar 2021) evaluating actual and/or perceived understanding of GS/ES among parents of a child with a symptomatic health condition offered GS/ES, in research, clinical, or hybrid contexts. Exclusions: studies on pre-symptomatic adult-onset testing, prenatal testing, or reproductive decision contexts, and non-parent samples. Records were managed in EndNote X9; screening performed independently by two reviewers (Rayyan) with consensus resolution. Interrater reliability: abstracts (Cohen’s kappa 0.76; 98% initial agreement), full texts (kappa 0.36; 65% initial agreement). Study quality and risk of bias assessed using the Mixed Methods Appraisal Tool (MMAT); all included studies were high quality. Data extraction covered study design, aims, measures of understanding, sequencing type, context, sample sociodemographics, timing relative to return of results, counseling provided, and key findings. Due to heterogeneity, meta-analysis was not performed; results were synthesized narratively and organized, where possible, using Ayuso et al.’s informed consent framework.

- Study selection and scope: From 1264 unique records, 16 studies met inclusion criteria. Of these, 15 evaluated actual understanding and six assessed perceived understanding. Total N=1487 parents (range 16–570 per study) across diverse pediatric conditions and clinical trajectories. Many parents had prior genetics exposure; at least five studies reported ≥65% with prior testing/coursework. Genetic counseling or information sessions commonly accompanied consent. - Actual understanding – scope and concepts: Parents often recognized ES/GS as more comprehensive than prior tests and that trio testing may be used; some viewed it simplistically as a blood test or general diagnostic tool. Understanding was mixed regarding differences between ES/GS and other tests, depth of analysis, higher likelihood of secondary findings with ES, and timelines for results. Many demonstrated good grasp of basic genomic principles (DNA-genes-health, inheritance), variant inheritance patterns, and that detected variants may not be causative. Lower understanding included de novo variants, protective variants, somatic versus germline distinctions, and implications of a negative result not excluding a genetic etiology or sibling risk. - Understanding of returned results: Parents in qualitative studies could accurately describe clinical significance, inheritance, and implications; however, many could not name the gene and some misconstrued the meaning of negative findings. - Benefits and risks: Parents understood potential benefits including diagnosis/prognosis clarification, potential to change management (treatment selection, surveillance, additional testing, palliation), and psychological benefits (curiosity satisfaction, relief of guilt, peace of mind, future preparation). Risks understood included no guarantee of actionable results, potential for unfavorable prognostic information, psychological distress, and implications for family members. - Privacy, confidentiality, and future data use: Understanding varied regarding insurance discrimination risks and legal protections; some US parents were unaware of GINA but recognized risks beyond its scope. Parents in research contexts understood contributions to advancing care, potential data storage in national databases, access by research/commercial entities, de-identification, and raised ethical concerns about downstream uses. - Secondary findings (SFs): Over half of parents in one survey (n=53) correctly answered ≥7/9 SF-related questions; many recognized low likelihood of SFs and potential utility for preparation and family testing/history confirmation. Misunderstandings included believing SFs could include non-health traits (e.g., height, hair color), uncertainty about which SFs would be reported, and ambiguity about autonomy/options for SF return. - Perceived understanding: Mixed results. Some parents reported understanding most consent elements (e.g., voluntariness, who is tested, benefits, SF options) “mostly” or well; less confidence about discrimination risks and SF implications. Trust in clinicians sometimes supplanted perceived need to understand all details. Parents more often reported understanding negative results than positive. Baseline actual understanding correlated with later perceived understanding in one study; increases in genomic knowledge were marginally associated with perceived understanding. - Associated factors: Higher actual understanding associated with higher education, baseline genetics knowledge, health literacy, income, English proficiency, non-Hispanic White ethnicity, and greater acculturation; one study found no association with ethnicity, age, sex, cure likelihood, treatment recommendation, or perceived understanding. Parents from genetics clinics reported higher perceived understanding than those from other specialty clinics, with similar actual understanding. - Impact of counseling: Two US studies reported that genetic counseling consultations were associated with significant increases in actual genomic knowledge; however, some misunderstandings persisted (e.g., somatic vs germline) and gains plateaued across repeated assessments.

The review demonstrates that while parents often appreciate potential benefits and applications of pediatric GS/ES, understanding is variable and sometimes superficial or inaccurate in key domains (e.g., secondary findings, privacy, somatic vs germline distinctions, implications of negative results). These findings address the research question by identifying specific knowledge strengths and gaps, highlighting the importance of targeted consent processes and educational supports. Unrealistic expectations can occur, influenced by prior unsuccessful testing, emotional distress, and emphasis on benefits during clinical discussions. Genetic counseling and tailored communication appear to improve knowledge but may not fully eliminate persistent misunderstandings. Ensuring alignment between actual and perceived understanding is critical for informed decision-making and may enhance satisfaction with care. The results underscore the need for healthcare professionals to assess and address parents’ informational needs, consider cultural and linguistic factors, and manage expectations about diagnostic yield and clinical utility.

Parents commonly recognize potential benefits of GS/ES for their child but have mixed understanding of associated risks, especially around secondary findings and data use beyond clinical care. Variability in perceived understanding is notable, with some parents reporting difficulty comprehending GS/ES information. Genetic counseling can improve actual understanding, though some misconceptions persist. The review suggests clinicians should proactively support parents’ comprehension of GS/ES and its implications for their child and family. Future research should comprehensively assess both actual and perceived understanding using validated tools, evaluate interventions (e.g., structured counseling), and examine relationships among information satisfaction, perceived understanding, and psychosocial outcomes.

The review is limited to English-language studies and to parents of pediatric patients offered or undergoing GS/ES. Heterogeneity in methodologies, outcomes, disease contexts, and counseling approaches precluded meta-analysis and limited cross-study comparability and depth assessments. Studies assessed understanding at different points in the diagnostic journey, complicating temporal comparisons. Measures of perceived understanding were fewer and could not be organized within the same framework as actual understanding. Limited reporting on recruitment settings and counseling content constrained analyses of contextual influences.