Exploration of transitional life events in individuals with Friedreich ataxia: Implications for genetic counseling

<p>Abstract</p> <p>Background</p> <p>Human development is a process of change, adaptation and growth. Throughout this process, transitional events mark important points in time when one's life course is significantly altered. This study captures transitional life events brought about or altered by Friedreich ataxia, a progressive chronic illness leading to disability, and the impact of these events on an affected individual's life course.</p> <p>Methods</p> <p>Forty-two adults with Friedreich ataxia (18-65y) were interviewed regarding their perceptions of transitional life events. Data from the interviews were coded and analyzed thematically using an iterative process.</p> <p>Results</p> <p>Identified transitions were either a direct outcome of Friedreich ataxia, or a developmental event altered by having the condition. Specifically, an awareness of symptoms, fear of falling and changes in mobility status were the most salient themes from the experience of living with Friedreich ataxia. Developmental events primarily influenced by the condition were one's relationships and life's work.</p> <p>Conclusions</p> <p>Friedreich ataxia increased the complexity and magnitude of transitional events for study participants. Transitional events commonly represented significant loss and presented challenges to self-esteem and identity. Findings from this study help alert professionals of potentially challenging times in patients' lives, which are influenced by chronic illness or disability. Implications for developmental counseling approaches are suggested for genetic counseling.</p> <p>Background</p> <p>Human development can be described in terms of key transitional events, or significant times of change. Transitional events initiate shifts in the meaning or direction of life and require the individual to develop skills or utilize coping strategies to adapt to a novel situation <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr></abbrgrp>. A successful transition has been defined as the development of a sense of mastery over the changed event <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Transitions can be influenced by a variety of factors including one's stage of development, such as graduation from high school, historical events, including war, and idiosyncratic factors, such as health status <abbrgrp><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr></abbrgrp>. Of particular interest in the present study are transitional life events, brought about or altered by progressive chronic illness and disability, and the impact of these events on the lives of affected individuals.</p> <p>It has been recognized that the clinical characteristics of a chronic illness or disability may alter the course and timing of many developmentally-related transitional events <abbrgrp><abbr bid="B6">6</abbr></abbrgrp>. For example, conditions associated with a shortened lifespan may cause an individual to pursue a career with a shorter course of training <abbrgrp><abbr bid="B6">6</abbr></abbrgrp>. Specific medical manifestations may also promote a lifestyle incongruent with developmental needs <abbrgrp><abbr bid="B6">6</abbr><abbr bid="B7">7</abbr></abbrgrp>. For example, an adolescent with a disability may have difficulty achieving autonomy because of his/her physical dependence on others.</p> <p>In addition to the aforementioned effects of chronic illness and disability on developmentally-related transitional events, a growing body of literature has described disease-related transitional events: those changes that are a direct result of chronic illness and disability. Diagnosis has received attention as being a key disease-related transitional event <abbrgrp><abbr bid="B8">8</abbr><abbr bid="B9">9</abbr></abbrgrp>. Studies have also noted other disease transitions related to illness trajectory <abbrgrp><abbr bid="B10">10</abbr></abbrgrp>, as the clinical features of the disease may require the individual to make specific adaptations. Disease-related events have also been described in terms of accompanying psychological processes, such as one's awareness of differences brought about by illness <abbrgrp><abbr bid="B11">11</abbr></abbrgrp>.</p> <p>While disease-related events are seemingly significant, the patient's perception of the events is varied. Some events may be perceived as positive experiences for the individual. For example, a diagnosis may end years of uncertainty. Some individuals may perceive these transitional events as insignificant, as they have accommodated to the continual change brought about by a chronic disease <abbrgrp><abbr bid="B12">12</abbr><abbr bid="B13">13</abbr></abbrgrp>.</p> <p>The aforementioned impact of disability and chronic illness on transitional events may create psychological stress. Developed by Lazarus and Folkman, the Transitional Model of Stress and Coping describes the process of adaptation to a health condition <abbrgrp><abbr bid="B14">14</abbr></abbrgrp>. This model purports that individuals first appraise a stressor and then utilize a variety of coping strategies in order to meet the stressor's demands <abbrgrp><abbr bid="B14">14</abbr></abbrgrp>. Thus, in the context of chronic illness, the ability of the individual to cope successfully with the stress of a health threat contributes to the process of overall adaptation to the condition.</p> <p>The process of adaptation can be more complex when the chronic illness or disability is progressive. Each transition brought about or altered by the disability may also represent additional loss, including the loss of future plans, freedom in social life and the ability to participate in hobbies <abbrgrp><abbr bid="B15">15</abbr></abbrgrp>. These losses may be accompanied by grief, uncertainty, and a continual need for adaptation <abbrgrp><abbr bid="B16">16</abbr><abbr bid="B17">17</abbr></abbrgrp>.</p> <p>Friedreich ataxia (FRDA) is one example of a progressive disorder, leading to adolescent and adult onset disability. To better understand patients' perceptions of key transitional events and the factors perceived to facilitate progression through these events, individuals with FRDA were interviewed.</p> <p>FRDA is a rare, progressive, neurodegenerative disorder affecting approximately one in 30,000 people in the United States <abbrgrp><abbr bid="B18">18</abbr></abbrgrp>. It equally affects both men and women. Individuals with FRDA experience progressive muscle weakness and loss of coordination in the arms and legs. For most patients, ataxia leads to motor incapacitation and full-time use of a wheelchair, commonly by the late teens or early twenties. Other complications such as vision and hearing impairment, dysarthria, scoliosis, diabetes mellitus and hypertrophic cardiomyopathy may occur <abbrgrp><abbr bid="B19">19</abbr><abbr bid="B20">20</abbr></abbrgrp>. Cardiomyopathy and respiratory difficulties often lead to premature death at an average age of 37 years <abbrgrp><abbr bid="B21">21</abbr></abbrgrp>. Currently, there are no treatments or cures for FRDA. Little is known about the specific psychological or psychosocial effects of the condition.</p> <p>FRDA is an autosomal recessive condition. The typical molecular basis of Friedreich ataxia is the expansion of a GAA trinucleotide repeat in both copies of the <it>FXN </it>gene <abbrgrp><abbr bid="B22">22</abbr></abbrgrp>. Age of onset usually occurs in late childhood or early adolescence. However, the availability of genetic testing has identified affected individuals with an adult form of the condition. This late-onset form is thought to represent approximately 10-15% of the total FRDA population <abbrgrp><abbr bid="B23">23</abbr></abbrgrp>.</p> <p>Health care providers of individuals with progressive, neurodegenerative disorders can help facilitate their patients' progression through transitional events. Data suggest that improvements should be made in the care of these individuals. Shaw et al. <abbrgrp><abbr bid="B24">24</abbr></abbrgrp> found that individualized care that helps to prepare patients for transition is beneficial. Beisecker et al. <abbrgrp><abbr bid="B25">25</abbr></abbrgrp> found that patients desire not only physical care from their providers, but also emotional and psychosocial support.</p> <p>Genetic counselors have an important opportunity to help patients with neuromuscular disorders progress through transitional events, as several of these conditions have a genetic etiology. Genetic counselors in pediatric and adult settings often develop long-term relationships with patients, due to follow-up care. This extended relationship is becoming increasingly common as genetic counselors move into various medical sub-specialties, such as neurology, ophthalmology, oncology and cardiology.</p> <p>The role of the genetic counselor in addressing the psychosocial needs of patients has been advocated, but rarely framed in the context of developmental events <abbrgrp><abbr bid="B26">26</abbr></abbrgrp>. Data suggest that patients may not expect a genetic counselor to address psychosocial needs <abbrgrp><abbr bid="B27">27</abbr></abbrgrp>. In a survey of genetic counseling patients, Wertz <abbrgrp><abbr bid="B28">28</abbr></abbrgrp> found a majority of respondents understood genetic conditions to have a moderate to serious effect on family life and finances, while almost half perceived there to be an effect on the spouse, quality of life, and the relationship between home and work. However, these topics were reportedly not discussed within genetic counseling sessions <abbrgrp><abbr bid="B27">27</abbr><abbr bid="B28">28</abbr></abbrgrp>. Overall, there is limited information about the experiences of transitional life events in FRDA, as well as a lack of recommendations for genetic counselors and other health care providers to assist patients through these events.</p> <p>Our study investigated perceptions of patients with Friedreich ataxia to 1) identify key transitional events and specific needs associated with events; 2) describe perception of factors to facilitate progression through the identified events; and 3) explore the actual or potential role of the health care provider in facilitating adaptation to the identified events. Data were used to make suggestions for developmental genetic counseling approaches in the context of ongoing care of clients with hereditary, progressive, neurodegenerative conditions.</p

Adaptation to bipolar disorder and perceived risk to children: a survey of parents with bipolar disorder

Abstract Background Bipolar disorder (BPD) is a common condition associated with significant morbidity and reduced quality of life. In addition to challenges caused by their mood symptoms, parents affected with BPD harbor concerns about the mental health of their children. Among adult parents who perceive themselves to have BPD, this study aims to examine participants’ coping methods; identify predictors of adaptation; assess parental perceptions of risks for mood disorders among their children; and describe the relationships among illness appraisals, coping, adaptation to one’s own illness, and perceived risk to one’s children. Methods Parents who self-identified as having BPD completed a web-based survey that assessed dispositional optimism, coping, perceived illness severity, perceived etiology of BPD, perceived risk to offspring, and adaptation to BPD. Participants had at least one unaffected child who was 30 years of age or below. Results 266 parents were included in the analysis. 87% of parents endorsed a “somewhat greater” or “much greater” risk for mood disorders in one’s child(ren) than someone without a family history. Endorsing a genetic/familial etiology to BPD was positively correlated with perceived risk for mood disorders in children (r s = .3, p < 0.01) and active coping with BDP (r = .2, p < 0.01). Increased active coping (β = 0.4, p < 0.001) and dispositional optimism (β = 0.3, p < 0.001) were positively associated with better adaptation, while using denial coping was negatively associated with adaptation (β = −0.3, p < 0.001). The variables explained 55.2% of the variance in adaptation (F = 73.2, p < 0.001). Coping mediated the effect of perceived illness severity on adaptation. Conclusions These data inform studies of interventions that extend beyond symptom management and aim to improve the psychological wellbeing of parents with BPD. Interventions targeted at illness perceptions and those aimed at enhancing coping should be studied for positive effects on adaptation. Parents with BPD may benefit from genetic counseling to promote active coping with their condition, and manage worry about perceived risk to their children

Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group

The routine use of genomic sequencing in clinical medicine has the potential to dramatically alter patient care and medical outcomes. To fully understand the psychosocial and behavioral impact of sequencing integration into clinical practice, it is imperative that we identify the factors that influence sequencing-related decision making and patient outcomes. In an effort to develop a collaborative and conceptually grounded approach to studying sequencing adoption, members of the National Human Genome Research Institute's Clinical Sequencing Exploratory Research Consortium formed the Outcomes and Measures Working Group. Here we highlight the priority areas of investigation and psychosocial and behavioral outcomes identified by the Working Group. We also review some of the anticipated challenges to measurement in social and behavioral research related to genomic sequencing; opportunities for instrument development; and the importance of qualitative, quantitative, and mixed-method approaches. This work represents the early, shared efforts of multiple research teams as we strive to understand individuals' experiences with genomic sequencing. The resulting body of knowledge will guide recommendations for the optimal use of sequencing in clinical practice

Psychological outcomes in advanced cancer patients after receiving genomic tumor profiling results

Background: Comprehensive tumor genomic profiling (CGP) offers hope for personalized treatment for cancer patients when other treatment options have been exhausted. However, receipt of nonactionable or ambiguous results could be an ongoing source of distress. We investigated patterns of hope, anxiety, depression, and CGP-specific anxiety in advanced cancer patients after receiving CGP results and 2–3months later. Method: Participants were enrolled in a longitudinal psychosocial substudy, embedded in the Molecular Screening and Therapeutics Program, and had advanced solid cancers of any histological type with sufficient and accessible tissue for CGP. At T0 (before receiving CGP results), 1,431 participants completed sociodemographic, disease and psychosocial measures. At T1 (1–4 weeks after receiving CGP results) and T2 (2–3 months post-T1), 374 participants completed psychological outcome measures. Predictors of outcomes at T2 were identified using multinomial logistic regression. Results: Approximately 75% of participants did not experience significant hopelessness or distress at T1 and T2.Hope decreased by T2, yet general anxiety and CGP-specific anxiety also decreased. Receiving actionable results did not impact psychological outcomes at T2. At T2, lower hope, and higher anxiety, depression and CGP-specific anxiety were associated with lower self-efficacy. Psychological and demo-graphic factors (age, socioeconomic status, language, medical occupation, urban living, family history of cancer) independently predicted one or more psychological trajectories. Worse health status and perceived susceptibility to cancer progression predicted hope and anxiety trajectories. Conclusion: Further research on interventions to best support patients undergoing CGP with high anxiety, hopelessness, fear of cancer progression, and poorer health is urgently needed

Development and validation of the Psychological Adaptation Scale (PAS): Use in six studies of adaptation to a health condition or risk

We introduce The Psychological Adaptation Scale (PAS) for assessing adaptation to a chronic condition or risk and present validity data from six studies of genetic conditions

Molecular genetic identification of skeletal remains from the Second World War Konfin I mass grave in Slovenia

This paper describes molecular genetic identification of one third of the skeletal remains of 88 victims of postwar (June 1945) killings found in the Konfin I mass grave in Slovenia. Living relatives were traced for 36 victims. We analyzed 84 right femurs and compared their genetic profiles to the genetic material of living relatives. We cleaned the bones, removed surface contamination, and ground the bones into powder. Prior to DNA isolation using Biorobot EZ1 (Qiagen), the powder was decalcified. The nuclear DNA of the samples was quantified using the real-time polymerase chain reaction method. We extracted 0.8 to 100 ng DNA/g of bone powder from 82 bones. Autosomal genetic profiles and Y-chromosome haplotypes were obtained from 98% of the bones, and mitochondrial DNA (mtDNA) haplotypes from 95% of the bones for the HVI region and from 98% of the bones for the HVII region. Genetic profiles of the nuclear and mtDNA were determined for reference persons. For traceability in the event of contamination, we created an elimination database including genetic profiles of the nuclear and mtDNA of all persons that had been in contact with the skeletal remains. When comparing genetic profiles, we matched 28 of the 84 bones analyzed with living relatives (brothers, sisters, sons, daughters, nephews, or cousins). The statistical analyses showed a high confidence of correct identification for all 28 victims in the Konfin I mass grave (posterior probability ranged from 99.9% to more than 99.999999%)

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

A first update on mapping the human genetic architecture of COVID-19

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