Search

Although genomic research offering next-generation sequencing (NGS) has increased the diagnoses of rare/ultra-rare disorders, populations experiencing health disparities infrequently participate in these studies. The factors underlying non-participation would most reliably be ascertained from individuals who have had the opportunity to participate, but decline. We thus enrolled parents of children and adult probands with undiagnosed disorders who had declined genomic research offering NGS with return of results with undiagnosed disorders (Decliners, n = 21) and compared their data to those who participated (Participants, n = 31). We assessed: (1) practical barriers and facilitators, (2) sociocultural factors-genomic knowledge and distrust, and (3) the value placed upon a diagnosis by those who declined participation. The primary findings were that residence in rural and medically underserved areas (MUA) and higher number of barriers were significantly associated with declining participation in the study. Exploratory analyses revealed multiple co-occurring practical barriers, greater emotional exhaustion and research hesitancy in the parents in the Decliner group compared to the Participants, with both groups identifying a similar number of facilitators. The parents in the Decliner group also had lower genomic knowledge, but distrust of clinical research was not different between the groups. Importantly, despite their non-participation, those in the Decliner group indicated an interest in obtaining a diagnosis and expressed confidence in being able to emotionally manage the ensuing results. Study findings support the concept that some families who decline participation in diagnostic genomic research may be experiencing pile-up with exhaustion of family resources - making participation in the genomic research difficult. This study highlights the complexity of the factors that underlie non-participation in clinically relevant NGS research. Thus, approaches to mitigating barriers to NGS research participation by populations experiencing health disparities need to be multi-pronged and tailored so that they can benefit from state-of -the art genomic technologies., (© 2023 National Society of Genetic Counselors.)

The Genome Empowerment Scale (GEmS), developed as a research tool, assesses perspectives of parents of children with undiagnosed disorders about to undergo exome or genome sequencing related to the process of empowerment. We defined genomic healthcare empowerment as follows: perceived ability to understand and seek new information related to the genomic sequencing, manage emotions related to the diagnostic process and outcomes, and utilize genomic sequencing information to the betterment of the individual/child and family. The GEmS consists of four scales, two are primarily emotion-focused (Meaning of a Diagnosis, and Emotional Management of the Process) and two are action-oriented (Seeking Information and Support, and Implications and Planning). The purpose of this research was to provide a strategy for interpreting results from the GEmS and present illustrative cases. These illustrations should serve to facilitate use of the GEmS in the clinical and research arena, particularly with respect to guiding genetic counseling processes for parents of children with undiagnosed conditions., (© 2021 National Society of Genetic Counselors.)

Background: Despite growing evidence of diagnostic yield and clinical utility of whole exome sequencing (WES) in patients with undiagnosed diseases, there remain significant cost and reimbursement barriers limiting access to such testing. The diagnostic yield and resulting clinical actions of WES for patients who previously faced insurance coverage barriers have not yet been explored., Methods: We performed a retrospective descriptive analysis of clinical WES outcomes for patients facing insurance coverage barriers prior to clinical WES and who subsequently enrolled in the Undiagnosed Diseases Network (UDN). Clinical WES was completed as a result of participation in the UDN. Payer type, molecular diagnostic yield, and resulting clinical actions were evaluated., Results: Sixty-six patients in the UDN faced insurance coverage barriers to WES at the time of enrollment (67% public payer, 26% private payer). Forty-two of 66 (64%) received insurance denial for clinician-ordered WES, 19/66 (29%) had health insurance through a payer known not to cover WES, and 5/66 (8%) had previous payer denial of other genetic tests. Clinical WES results yielded a molecular diagnosis in 23 of 66 patients (35% [78% pediatric, 65% neurologic indication]). Molecular diagnosis resulted in clinical actions in 14 of 23 patients (61%)., Conclusions: These data demonstrate that a substantial proportion of patients who encountered insurance coverage barriers to WES had a clinically actionable molecular diagnosis, supporting the notion that WES has value as a covered benefit for patients who remain undiagnosed despite objective clinical findings., (© 2019 National Society of Genetic Counselors.)

The "diagnostic odyssey" is well known and described in genetic counseling literature. Studies addressing the psychological, emotional, and financial costs of not having a diagnosis have shown how it permeates the lives of patients and families. The Undiagnosed Diseases Network aims to end this odyssey by providing diagnoses to individuals with undiagnosed conditions through multidisciplinary evaluations, whole exome and genome sequencing, and basic science research. It also provides an opportunity to learn from patients and families and to better understand their journeys and the impact of receiving a diagnosis. Seven cases are presented that outline challenges that come from working with chronically undiagnosed and newly diagnosed patients in a time when sequencing for clinical diagnosis is rapidly increasing. They illuminate the emotional journey of patients and families searching for a diagnosis and the mental health problems, financial distress, and chaos that can accompany not having answers. They also illustrate the surprising reactions patients and families can have to receiving a diagnosis, including anger, grief, and disappointment. While the lessons learned from these families are not novel, new strategies are presented for handling these challenges in undiagnosed and ultra-rare populations, groups that will increase with the rise of clinical sequencing., (© 2019 National Society of Genetic Counselors.)

The burden of living with an undiagnosed condition is high and includes physical and emotional suffering, frustrations, and uncertainty. For patients and families experiencing these stressors, higher levels of empowerment may be associated with better outcomes. Thus, it is important to understand the experiences of patients with undiagnosed conditions and their families affected by undiagnosed conditions in order to identify strategies for fostering empowerment. In this study, we used the Genetic Counseling Outcome Scale (GCOS-24) to assess levels of empowerment and support group participation in 35 adult participants and 67 parents of child participants in the Undiagnosed Diseases Network (UDN) prior to their UDN in-person evaluation. Our results revealed significantly lower empowerment scores on the GCOS-24 in adult participants compared to parents of child participants [t(100) = - 3.01, p = 0.003, average difference = - 11.12, 95% CI (- 3.78, - 18.46)] and no significant association between support group participation and empowerment scores. The majority of participants (84.3%, 86/102) are not currently participating in any support groups, and participation rates were not significantly different for adult participants and parents of child participants (11.4 vs. 19.7%, respectively, FE p = 0.40). Open-ended responses provided additional insight into support group participation, the challenges of living with undiagnosed conditions, and positive coping strategies. Future research will evaluate the extent to which empowerment scores change as participation in the UDN unfolds.

Little is known about the psychosocial profiles of parents who have a child with an undiagnosed chronic illness. The National Institutes of Health Undiagnosed Diseases Network (UDN) evaluates individuals with intractable medical findings, with the objective of discovering the underlying diagnosis. We report on the psychosocial profiles of 50 parents whose children were accepted to one of the network's clinical sites. Parents completed questionnaires assessing anxiety, depression, coping self-efficacy, and health care empowerment at the beginning of their child's UDN clinical evaluation. Parents of undiagnosed children had high rates of anxiety and depression (~ 40%), which were significantly inversely correlated with coping self-efficacy, but not with health care empowerment. Coping self-efficacy, depressive, and anxiety symptoms were better in parents with older children and with longer duration of illness. Gender differences were identified, with mothers reporting greater health care engagement than fathers. Overall, our findings suggest that parents of children with undiagnosed diseases maintain positive coping self-efficacy and remain actively engaged in health care and to a lesser degree tolerance for uncertainty, but these come with a high emotional cost to the parents. As the parents' psychological needs may not be obvious, these should be ascertained and the requisite support provided.

Due to the lack of empirical information on parental perceptions of primary results of whole exome sequencing (WES), we conducted a retrospective semi-structured interview with 19 parents of children who had undergone WES. Perceptions explored during the interview included factors that would contribute to parental empowerment such as: parental expectations, understanding of the WES and results, utilization of the WES information, and communication of findings to health/educational professionals and family members. Results of the WES had previously been communicated to families within a novel framework of clinical diagnostic categories: 5/19 had Definite diagnoses, 6/19 had Likely diagnoses, 3/19 had Possible diagnosis and 5/19 had No diagnosis. All parents interviewed expressed a sense of duty to pursue the WES in search of a diagnosis; however, their expectations were tempered by previous experiences with negative genetic testing results. Approximately half the parents worried that a primary diagnosis that would be lethal might be identified; however, the hope of a diagnosis outweighed this concern. Parents were accurately able to summarize their child's WES findings, understood the implications for recurrence risks, and were able to communicate these findings to family and medical/educational providers. The majority of those with a Definite/Likely diagnosis felt that their child's medical care was more focused, or there was a reduction in worry, despite the lack of a specific treatment. Irrespective of diagnostic outcome, parents recommended that follow-up visits be built into the process. Several parents expressed a desire to have all variants of unknown significance (VUS) reported to them so that they could investigate these themselves. Finally, for some families whose children had a Definite/Likely diagnosis, there was remaining frustration and a sense of isolation, due to the limited information that was available about the diagnosed rare disorders and the inability to connect to other families, suggesting that for families with rare genetic disorders, the diagnostic odyssey does not necessarily end with a diagnosis. Qualitative interviewing served a meaningful role in eliciting new information about parental motivations, expectations, and knowledge of WES. Our findings highlight a need for continued communication with families as we navigate the new landscape of genomic sequencing.

Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an increased chance of developing a psychiatric disorder. While parents of children affected by 22q11.2DS typically receive counseling about risk for non-psychiatric health concerns, genetic counselors may be reluctant to discuss psychiatric risk. Further education of genetic counselors may be necessary to encourage discussion of psychiatric risk with these families. The goal of this project was to develop recommendations for genetic counselors to provide psychiatric risk information to families affected by 22q11.2DS. The recommendations were developed by synthesizing resources in the literature about risk communication. These recommendations were refined following an online focus group meeting with five health care professionals who were recruited for participation from 22q11.2DS clinics across the U.S.A. The focus group data revealed three themes related to discussion of psychiatric risk: 1) Stepwise approach, 2) Discussing treatment options and reducing risks, and 3) Addressing stigma. These recommendations may be used as a foundation for a future clinical protocol to encourage discussion about the risk for psychiatric illness at an earlier point in the diagnostic process for 22q11.2DS and to provide improved information, support and resources to affected families.

22q11.2 deletion syndrome (22q11DS) is the most common microdeletion in humans. There have been few studies assessing the impact of this condition on the family and no previous studies conducted on unaffected siblings of children with 22q11DS. The goal of this study was to determine the frequency, method, and content of information being communicated by parents to unaffected siblings about the condition and to assess unaffected siblings' knowledge of 22q11DS and perceptions of the impact of the condition on their affected sibling and themselves. Families were recruited from several 22q11DS educational and support organizations and asked to complete a single anonymous online survey. Families were eligible to participate if they had one child with 22q11DS and at least one unaffected child between the ages of 12 and 17. Survey questions were developed based on previous literature and authors' expertise with individuals with 22q11DS. Responses to quantitative and qualitative questions were analyzed to calculate frequencies and proportions and to extract themes, respectively. A total of 25 families (defined as a unit of at least one parent, one affected child, and at least one unaffected child) participated in the study. Parents shared genetic information less often as compared to behavioral and medical information. Siblings of children with 22q11DS had both positive and negative experiences in having a brother or sister with this condition. Genetic counselors can use the results of this study to develop anticipatory guidance for parents of children with 22q11DS in talking with their unaffected children about the condition.

Most children with chromosome 22q11.2 deletion syndrome (22q11DS) have an IQ in the range that may allow them to be capable of understanding a genetic diagnosis despite mild intellectual disabilities. However, there are no publications that relate to the disclosure of a 22q11DS diagnosis to the affected child, or the factors that influence parents' disclosure to the child. A pilot study was conducted including eight semi-structured interviews with caregivers of children with 22q11DS, 10 to 17 years of age, to investigate the factors that influence how parents inform their children of the diagnosis. Six of eight participants had disclosed the diagnosis to the child, and most of these parents felt they could have benefited from additional advice from professionals to increase their confidence and success, as well as the child's comprehension of the information. Those who had not informed the child were uncertain about the words to use, how to initiate the conversation, or were concerned about the child's level of understanding. Our results demonstrate that genetics professionals should help prepare caregivers for conversations with their children about the diagnosis of 22q11DS, monitor the understanding of the diagnosis over time, and provide ongoing support.

The purpose of this study is to examine the association between parental socio-economic status (SES) and childhood neurocognition and behavior in children with chromosome 22q11.2 deletion syndrome (22q11DS). Although undoubtedly, the deletion of genes in the 22q11.2 interval is primarily responsible for the psychological manifestations, little is known about the role of the environment in either mitigating or contributing to these problems. We examined the association of parental socio-economic status (SES) with cognition and behavior in children with 22q11DS (n = 65) and matched healthy control subjects (n = 52), since SES is a component of family resources. We found that in children with 22q11DS, higher SES correlated with better overall functioning (p < .01) and social skills (p < .01), and less frequent oppositional defiant behavior (p < .001). These findings were in contrast to the control subjects in whom SES correlated with cognition and achievement, but not behavior. Our results indicate that environmental factors influence the behavioral phenotype in children with 22q11DS, providing a framework for developing appropriate interventions. As such, genetic counseling for families with 22q11DS may include consideration of family resources and inclusion of other health professionals, such as social workers, to explore with the family available social supports and resources.