Research

Abstract:

Background: The integration of somatic and germline genetic testing has become increasingly central to pediatric oncology care, offering opportunities for personalized treatment and identification of hereditary cancer risk. However, families often receive this information during a highly stressful period, and limited research has examined how they experience and interpret genetic testing in real-world clinical settings, particularly in medically underserved populations. Methods: This qualitative study explored the experiences of parents of pediatric oncology patients who underwent dual germline and somatic genetic testing at Valley Children’s Hospital in California’s Central Valley. Semi-structured interviews were conducted in both English and Spanish following results disclosure with nine participants. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis to identify recurring patterns in understanding, emotional responses, communication experiences, and informational needs. Results: Five major themes emerged: (1) emotional burden associated with uncertainty and waiting, (2) incomplete understanding of genetic testing and results, (3) fragmented communication and lack of follow-up, with ongoing uncertainty despite testing identified as a subtheme, (4) parent responsibility for interpreting and sharing genetic information, and (5) challenges in accessing clear and consistent information. Participants described genetic testing as an evolving process rather than a single event, often marked by persistent uncertainty, difficulty retaining information, and reliance on external sources to fill informational gaps. 4 Conclusions: Germline genetic testing in pediatric oncology is experienced by families as a complex, ongoing process marked by uncertainty, communication challenges, and unmet informational needs. These findings highlight the importance of integrating genetic counseling into oncology care, improving communication workflows, and providing structured follow-up and educational support. Enhancing these aspects of care may improve understanding, reduce uncertainty, and better support families as they navigate the clinical and psychosocial implications of genetic testing.

Abstract:

Measurement of the peak systolic velocity (PSV) through the fetal middle cerebral artery (MCA) using Doppler is a well-established screening tool for fetal anemia. However, the relationship between abnormally increased MCA Doppler and monogenic disease remains poorly understood. This research investigated whether unexplained MCA Doppler abnormalities are useful to predict the presence of an underlying monogenic etiology. Clarifying this relationship would help explain the unknown etiologies of nonanemic fetuses and those with severe clinical presentations. Finding a relationship could also elucidate novel genotype-phenotype associations and aid in predicting outcomes for fetuses at risk for monogenic diseases. A retrospective chart review used data from fetuses that underwent genetic evaluation at a tertiary medical center between 2015 and 2025. Inclusion criteria were fetuses with MCA Doppler measurement and exome sequencing (ES) results, regardless of anemia status. Variables collected included MCA- PSV values, gestational age, genetic diagnoses, hemoglobin levels, infectious disease results, structural anomalies, and clinical outcomes. A Fisher’s exact test was performed to determine whether a fetus having an abnormal or normal MCA Doppler result is independent of the fetal ES result. Analyses compared ES results in fetuses with abnormal versus normal-range MCA Doppler. Our findings suggest that MCA Doppler velocimetry is not associated with monogenic conditions in fetuses with clinical disorders. Findings of this research are important for prenatal genetic counseling as they provide a relevant context for genetic risk assessment in the diagnostically uncertain setting of suspected fetal anemia. Also, when immune etiologies for fetal anemia are excluded, considering possible genetic etiologies for all fetuses undergoing MCA Doppler as a next step can help clinicians develop a patient-centered approach to care for fetuses with both abnormal and normal MCA Doppler results. Keywords: Exome sequencing; Fetal anemia; Fetal Doppler; Genetic counseling; Middle cerebral artery peak systolic velocity.

Abstract:

The use of next-generation sequencing is rapidly expanding in the neonatal intensive care unit (NICU) to diagnose infants with rare genetic conditions. Although patients and their families rely on their providers for information and guidance, these providers may struggle to interpret complex genetic results and communicate their implications effectively. To address this gap, this study compares the communication and counseling skills of genetic counselors (GCs) and non- genetics providers (NGPs) using audio transcriptions of real return-of-result sessions for infants with features suggestive of an underlying genetic etiology. In the first phase of this study, a scoping literature review was conducted to better understand the research landscape and to develop an initial codebook for qualitative analysis. In the second phase, content analysis was used to compare the provider groups across different communication aspects. While both provider groups communicated similar information to families during the return-of-results sessions, they did so in different ways. GCs used less biased and ableist language (26% of GC transcripts vs. 48% of NGP transcripts), gave fewer disorganized explanations (0% vs. 43%), explained more medical terms (74% vs. 57%), and provided more context about the test performed (74% vs. 52%) than NGPs. These findings demonstrate that GCs are well-suited to assist families in the NICU in navigating complex genetic information and guiding them to appropriate care and resources. Additionally, we identified opportunities for training in genetic counseling programs, with greater attention needed on the use of educational aids and reducing dominance in communication. By improving communication training and utilizing GCs in the NICU, we hope to enhance patient and family experiences and the quality of care they receive.

Abstract:

Whole-genome sequencing (WGS) is increasingly used as a first-tier genetic test in both pediatric and adult clinics. As clinical use of WGS expands, understanding the long-term impact of genomic results remains understudied. The Perceived Understanding of Results, Autonomy, and Security of Care (PURASC) Study is a qualitative study to examine the experience of adult patients, one to three years after their initial genetics consult appointment from 2022-2025, who underwent both WGS and standard genetic testing (SGT) as part of the Adult Brain Cohort - Dissecting the Efficacy and Efficiency of First-line Genome sequencing (ABCDEFG) Study. WGS provides a comprehensive analysis of the entire genome, while SGT encompasses more targeted testing methods, including gene panels and exome sequencing, In Process which assess a limited portion of the genome. The PURASC study explored the perceived understanding of results, health autonomy, and access to healthcare after individuals received both WGS and SGT. Fifteen semi-structured interviews were conducted with individuals seen in the University of California, San Francisco Neurogenetics Clinic who had received both SGT and WGS results at least 11 months prior to their interview. Interviews were designed to expand upon prior survey-based research on the personal utility of genetic testing in this cohort by eliciting in-depth patient perspectives. Reflexive thematic analysis identified five main themes: understanding genetic results, emotional responses to testing, personal utility of genetic testing, healthcare access, and patient agency and engagement. Themes were characterized by assigned sentiment to capture nuanced variations in participant experiences. This study further supports prior literature that patients find value in WGS beyond clinical utility. Overall, participant sentiments were multifaceted and evolving, with many individuals reporting reassurance and personal utility from WGS while also describing persistent 4 uncertainty, emotional complexity, and healthcare access challenges.

Abstract:

Gould Syndrome, caused by variants in the COL4A1 and COL4A2 genes, is a rare, multisystemic condition characterized by cerebrovascular disease and a variety of neurological, ocular, renal, muscular, and cardiac abnormalities. The broad phenotypic spectrum and variable expressivity associated with Gould Syndrome, together with limited awareness and understanding of the natural history, creates challenges with the diagnosis and management of individuals and families affected with this ultra-rare condition. Previous research in other rare disease populations demonstrates the value of in-depth explorations of the experiences of parents as they navigate a diagnostic odyssey and a genetic diagnosis. This study aimed to deepen the understanding of families’ experiences and identify recommendations to expand awareness of Gould Syndrome and improve the care and identification of new patients and families. This qualitative study consisted of interviews with caregivers of children enrolled in the UCSF Gould Syndrome (COL4A1/2) Natural History Registry Study. Interview data were analyzed using reflexive thematic analysis to identify themes related to caregivers' experiences with the diagnostic odyssey, genetic testing, and the genetic diagnosis. Fourteen in-depth semi- structured interviews were conducted between August and November 2025. Six themes were identified across interviews to capture parents’ experiences and perspectives. These included: 1) The Value of a Genetic Diagnosis; 2) The Impacts of Limited Awareness and Understanding of Gould Syndrome; 3) The Importance of Motivated, Knowledgeable Healthcare Providers; 4) Parents are Experts and Advocates; 5) The Parent Experience is Emotionally Complex; and 6) Parent Support Communities are Valuable, but “A Double-edged Sword”. These insights highlight several areas of need within the Gould Syndrome community and inform recommendations for addressing these gaps and expanding awareness of Gould Syndrome.

Abstract:

Prenatal genetic counselors (GCs) may be vulnerable to compassion fatigue (CF) and burnout due to the emotional and ethically complex nature of their work. Abortion restrictions in the United States have placed additional stress on reproductive healthcare providers. While prior research suggests abortion legislation may impact the emotional well-being of GCs, no studies have directly examined the impact abortion laws have had on CF or burnout. Broadening this understanding is important to improve retention, practice outcomes, provider well-being, and assess how to best support prenatal GCs in their roles. This study aimed to explore whether prenatal GCs in abortion-restrictive states are at a greater risk of burnout and CF compared to those in protective states. It was hypothesized that prenatal GCs in abortion-restrictive states would exhibit higher levels of burnout and CF compared to those in protective states. A cross- sectional survey was developed using validated survey measures, abortion-specific questions, and open-ended questions based on themes identified in the literature. Responses from 151 prenatal GCs were analyzed using descriptive statistics, and open-ended questions were analyzed thematically. A comparative analysis was conducted between respondents in restrictive and protective policy environments. Participants reported consistently high levels of compassion satisfaction (CS) and low to moderate levels of burnout and CF. However, abortion-specific measures indicated higher burnout and CF among participants in protective and mixed policy states. Open-ended responses highlighted structural barriers, changes in counseling approaches, emotional implications of restrictions, comparisons of state legislation, and the coping strategies utilized by participants. Collectively, these findings indicate that strain associated with abortion care is influenced by a variety of factors beyond legislation, including uncertainty, capacity changes, and evolving clinical demands across different policy environments, highlighting the necessity for support and clear guidelines to enhance GC well-being.

Abstract:

Background: Cascade genetic testing is a key strategy for identifying at-risk relatives of individuals with hereditary cancer predisposition; however, uptake remains limited. While prior research has focused on barriers to testing, less is known about how individuals experience and navigate the process of communicating genetic risk within families. Purpose: This qualitative study explored how individuals with hereditary cancer risk perceive, approach, and experience disclosure of genetic information to relatives. Methods: This study was a qualitative sub-study within a digital cascade testing initiative at a single academic medical center (a web-based module supporting patient- or provider-facilitated family notification). Semi-structured interviews were conducted with seven adult probands carrying pathogenic variants in cancer-predisposition genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, or EPCAM). Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. Results: Five interconnected themes emerged. (1) Participants described a strong responsibility to inform relatives, often grounded in moral and relational considerations. (2) Family responses varied widely, influencing communication patterns and outcomes, with disclosure not consistently leading to cascade testing uptake. (3) Disclosure was an active, tailored, and ongoing process, shaped by relational dynamics and perceived readiness. (4) Family and cultural contexts shaped emotional and cognitive experiences. (5) Healthcare systems affected both understanding and disclosure practices, with genetic counseling and provider resources facilitating communication, though preferences for provider involvement varied. Conclusions: Disclosure of hereditary cancer risk is a dynamic, relational process rather than a single event. Although individuals often feel a strong obligation to share genetic information, variability in family responses and structural factors may limit downstream testing. Interventions may benefit from flexible, culturally responsive approaches that support ongoing communication and reduce patient burden.

Abstract:

Germline predisposition to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) carries significant clinical implications for diagnosis, treatment planning, allogeneic stem cell transplant donor selection, and familial risk assessment. Current National Comprehensive Cancer Network (NCCN) guidelines recommend germline genetic evaluation for all patients diagnosed with MDS or AML before age 50, as well as for those whose somatic testing reveals variants suspicious for germline origin, meaning every guideline-eligible patient should be referred for genetic counseling and considered for germline testing (NCCN Guidelines for MDS Version 2.2025). Despite these clear recommendations, integration into routine clinical practice remains inconsistent. This quality improvement study evaluated real-world utilization of germline genetic counseling and testing among 166 adult patients (age 18-49) who met the NCCN criteria for germline evaluation, representing a guideline-appropriate subset, not all patients with MDS/AML, seen at a single academic medical center between 2020 and 2025. Among this eligible population, only 17 of 166 patients (10%) were referred for genetic counseling, meaning that 90% of guideline- eligible patients were never referred, representing the primary gap identified in this study. Among those who were referred, the median time from the initial Hematology Oncology visit to Cancer Genetics referral was 78 days. Of the 17 referred patients, 81% completed germline evaluation, and 8% of the total eligible population ultimately completed germline testing. Notably, the high completion rate among those referred (81%) indicates that the critical failure point lies in referral initiation, not in patient follow-through. Strikingly, only 3 of 166 guideline- eligible patients (1.8%) were identified as carrying a pathogenic germline variant – well below the 13.6-20% prevalence reported in published literature – A finding that likely reflects the vii consequences of systematic under-referral rather than a true difference in underlying prevalence. Referral decisions were primarily driven by somatic testing results, particularly high variant allele frequency (VAF), rather than by guideline-based criteria such as age or family history. Provider feedback identified key barriers including inconsistent interpretation of guideline eligibility criteria, limited clinical capacity, and competing priorities in the context of time- sensitive hematologic disease management. Overall, germline evaluation was strikingly underutilized and largely reactive, driven by incidental somatic findings rather than proactive, criteria-based referral initiated early in the Hematology Oncology care pathway. These findings highlight the urgent need for standardized referral protocols, clearer provider education on NCCN eligibility criteria, and deeper integration of genetic counseling into hematologic oncology care, particularly given the direct implications for donor selection and familial risk in this patient population.

Abstract:

Variants of uncertain significance (VUSs) are a common and growing outcome of hereditary cancer genetic testing, yet they are among the most complex results to communicate and understand. Patients frequently misinterpret VUS results, which leads to distress, unnecessary medical action, or unwarranted dismissal. This underscores the need for effective communication tools. This quality improvement project aimed to develop a patient-centered VUS disclosure tool informed by the expertise of cancer genetic counselors. A national survey was distributed to clinical and laboratory genetic counselors via National Society of Genetic Counselors (NSGC) and American Board of Genetic Counseling (ABGC), and 185 responses were retained for analysis. Quantitative analysis examined misconceptions, emotional responses, disclosure strategies, and preferred tool elements, while thematic analysis of open-ended responses identified noteworthy challenges and additional desired features. The most reported patient misconception was that a VUS confers elevated cancer risk, the most frequently observed emotional response was disappointment with the lack of a definitive answer, and the most utilized disclosure strategy was offering reassurance. Genetic counselors prioritized inclusion of a simple explanation, along with clarification that a VUS should not guide medical decision- making. Thematic analysis further highlighted gene-phenotype matching as a prominent disclosure challenge, alongside a desire for reclassification update features and an accessible design. An educational pamphlet was developed based on these findings. It incorporated plain language, simple visuals, and content directly responsive to identified misconceptions and disclosure strategies. This tool represents an accurate and low-barrier resource to support VUS disclosure in oncology, and may serve as a foundation for improving patient understanding of VUS results.

Abstract:

Purpose: Disclosure of an individual’s hereditary cancer genetic testing results to relatives is crucial for family members health management, yet the experience of Southeast Asian (SEA) and SEA American individuals remain largely understudied compared to the broader Asian population. To better understand the experiences of SEA cancer genetics patients, we conducted a cross-sectional survey with closed and open-ended questions. Methods: Participants with a self-identified SEA background, who were able to take the survey in either English, Tagalog, or Vietnamese, were recruited from the UCSF Cancer Genetics Registry from October 2025 to January 2026. RStudio was utilized to analyze the survey data. Summary descriptive statistics were generated for the sample and comparative analyses were conducted using chi-square tests and Fisher’s exact test to examine correlation between demographic variables and disclosure status. Results: Respondents were predominantly female individuals aged 50 and older, with either a Filipino or Vietnamese identity. Of the 38 respondents, 84% reported disclosure of their results to family members. Key findings indicated that 1) participants reported high levels (>80%) of self-understanding regarding their results and perceived clinical utility, 2) participants primarily disclosed their results through in-person conversation and phone calls, with a higher disclosure rate to female relatives compared to male, and 3) a significant portion of participants chose ‘None’ concerning factors influencing non-disclosure and cultural considerations of disclosure. Statistical analysis revealed there was no statistical significance between factors such as identity, testing results, type, age, or ethnicity regarding disclosure. Conclusion: Findings from this study emphasize the importance of moving beyond broad, categorical understanding of populations to explore distinct ethnic experiences. For genetic counselors working with Filipino and Vietnamese individuals, approaching counseling from a collectivist lens is essential to help with familial communication.

Abstract:

Purpose: We explored the perspective of patients who have or are currently undergoing in vitro fertilization (IVF) regarding preimplantation genetic testing for polygenic conditions (PGT-P). Methods: We conducted semi-structured interviews (n=22) with patients who have or are currently undergoing IVF and have undergone or shown interest in PGT for aneuploidy (PGT-A) or monogenic conditions (PGT-M). Participants shared their experience with PGT, their viewpoints on PGT-P, and how or whether PGT-P should be used in reproductive decision- making. All participants were provided with technical information, benefits, and limitations about PGT-P during the interview. Inductive thematic analysis was used to analyze the interviews. Results: Participants held nuanced perspectives on PGT-P. Participants shared that PGT-P can provide information to help future children make future lifestyle adjustments and prevent certain polygenic conditions. Participants examined these benefits alongside the technology’s limitations and the harms it poses to patients, embryos, and society. Some participants expressed discomfort with the potential use of PGT-P for trait screening, while others thought the information could be informative for those with a personal or family history of the polygenic condition(s). Many participants had complex opinions about who, when, and how PGT-P should be offered. Some individuals proposed various stipulations, including extensive education, that should accompany the test if offered. Most participants also reported that they deferred the ultimate decision-making about whether to use PGT-P to their healthcare providers, positioning them as the gatekeepers of assisted reproductive technology (ART). Conclusion: This study shows that IVF patients held complex perspectives on PGT-P. Even though PGT-P was portrayed as a tool for screening for polygenic conditions, some participants expressed discomfort with the ethical implications of using the technology, particularly with screening for traits. These concerns were not significant enough for all participants to completely dismiss the technology for its benefits to other IVF patients who may want anticipatory guidance on child rearing. Many relied heavily on healthcare providers to act as gatekeepers for PGT-P and other ART forms. Because PGT-P and other emerging reproductive technologies are not heavily regulated by legislative policies, healthcare providers rely on professional guidelines and their own expert opinions to uphold the gatekeeper responsibilities. Therefore, further studies should be conducted to develop a more structured guideline as to when the various reproductive technologies are permissible and how they should be offered, with the ultimate goal of benefiting all involved stakeholders.

Abstract:

Prenatal exome sequencing (ES) and preimplantation genetic testing (PGT) are rapidly expanding in clinical and commercial settings despite ongoing uncertainty regarding their clinical utility and ethical implications. Little is known about how expanding prenatal genetic information shapes lived experiences of pregnancy, and healthcare professionals report a lack of confidence in navigating the associated complexities. This qualitative study examined whether exposure to a narrative-based podcast featuring diverse lived experiences and multidisciplinary perspectives influences first-year genetic counseling students' views on the utility and ethics of emerging prenatal genetic technologies. It evaluated the podcast's perceived value as an educational tool, and findings informed the development of a survey instrument for broader community engagement. Thirteen first-year genetic counseling students participated in two semi-structured focus groups following exposure to a 50-minute podcast episode exploring prenatal ES and PGT in clinically healthy pregnancies. Transcripts were analyzed using inductive thematic analysis. Four themes emerged: accessibility of the podcast as an audio-based learning format; bridging gaps in student education through patient narratives that enhanced conceptual understanding, counseling skills, and professional reflexivity; bridging gaps in public discourse by increasing awareness of clinical uncertainty, commercial influences, and limitations of emerging technologies; and patient empowerment through normalization of uncertainty and reinforcement of patient autonomy. Findings indicate that narrative-based media can meaningfully shift how future genetic counseling professionals interpret the ethical and clinical complexity of prenatal genetic technologies, particularly by broadening definitions of clinical utility beyond diagnostic outcomes toward psychosocial meaning. These findings support the integration of narrative-based approaches into genetics education and highlight the need for educational tools that foster ethical reflection, contextual understanding, and patient-centered decision-making.