Toward the diagnosis of rare childhood genetic diseases: what do parents value most?

Genomic testing is becoming routine for diagnosing rare childhood genetic disease. Evidence underlying sustainable implementation is limited, focusing on short-term endpoints such as diagnostic yield, unable to fully characterize patient and family valued outcomes. Although genomic testing is becoming widely available, evidentiary and outcomes uncertainty persist as key challenges for implementation. We examine whether the current evidence base reflects public tolerance for uncertainty for genomics to diagnose rare childhood genetic disease. We conducted focus groups with general population parents in Vancouver, Canada, and Oxford, United Kingdom, to discuss expectations and concerns related to genomic testing to diagnose rare childhood genetic disease. Applying a purposive sampling technique, recruitment continued until thematic saturation was reached. Transcripts were analysed using thematic analysis. Thirty-three parents participated across four focus groups. Participants valued causal diagnoses alongside management strategies to improve patient health and wellbeing. Further, participants valued expanding the evidence base to reduce evidentiary uncertainty while ensuring security of information. Willingness to pay out of pocket for testing reflected perceived familial health benefit. Diagnostic yield fails to fully capture valued outcomes, and efforts to resolve uncertainty better reflect public priorities. Evaluations of genomic testing that fully integrate valued endpoints are necessary to ensure consistency with best practices and public willingness to accept the uncertain familial benefit.

How Patient Perceptions Shape Responses and Outcomes in Inherited Cardiac Conditions.

At least one-third of adults living with an inherited cardiac condition report clinically-significant levels of psychological distress. Poorer health-related quality of life compared with population norms is also consistently reported. These outcomes are associated with younger patient age, having an implantable cardioverter defibrillator, and receipt of uncertain clinical test results, and can influence self-management behaviours, such as adherence to potentially critical life-preserving medications. According to the Common Sense Model of Illness, people use information from multiple sources to 'make sense' of their health condition, and how they conceptualise the condition can strongly influence adaptation and coping responses. Previous studies with people with inherited cardiac conditions show that illness perceptions, such as greater perceived consequences and a poorer understanding of the condition, are associated with greater psychological distress and poorer adherence to medication. The Common Sense Model provides one potential framework for identifying patients who may be more vulnerable to adverse health outcomes, and for developing early interventions to reduce the physical and psychosocial burden of these conditions. Interventions based on the Common Sense Model have successfully improved physical and psychosocial outcomes associated with other cardiac conditions, and could be tailored for use with patients with an inherited cardiac condition (ICC).

[Neurological appraisal of children and adolescents with psychotic symptoms]. / Valoracion neurologica de niños y adolescentes con sintomas psicoticos.

INTRODUCTION: Psychotic manifestations in childhood are not infrequent, yet the existing literature dealing with the neurological appraisal of children and adolescents with a clinical picture of psychosis is very scant. AIM: To conduct a non-systematic review of the literature that provides an answer to these three questions: When must a neurological appraisal be performed in a child with psychotic traits? What medical conditions can include signs and symptoms of psychosis in their development? And, what diagnostic procedure should be followed? DEVELOPMENT: The diseases that can present psychotic symptoms at onset or during their course are reviewed and grouped by pathologies: inborn errors of metabolism, genetic diseases, autoimmune and infectious diseases, malformations of the central nervous system, epilepsy, vascular pathology, rheumatologic processes, brain tumours, and psychoactive substances and drugs. A diagnostic regimen is proposed in which both the information obtained from the anamnesis and examination and the findings from each of the diagnostic tests are evaluated. CONCLUSIONS: A huge number of processes can display psychotic symptoms during their course and the key information offered by the anamnesis and examination must be taken into account. This review can help neuropaediatricians and other specialists perform a more systematised appraisal of children and adolescents with psychotic signs and symptoms.

TITLE: Valoracion neurologica de niños y adolescentes con sintomas psicoticos.Introduccion. Las manifestaciones psicoticas en la infancia no son infrecuentes; sin embargo, la bibliografia existente acerca de la valoracion neurologica de niños y adolescentes con cuadros psicoticos es muy escasa. Objetivo. Realizar una revision bibliografica no sistematica que permita responder a estas tres cuestiones: cuando debe llevarse a cabo una valoracion neurologica en un niño con rasgos psicoticos?, cuales son las condiciones medicas que pueden incluir un cuadro psicotico en su evolucion? y cual debe ser el procedimiento diagnostico? Desarrollo. Se revisan las enfermedades que pueden presentar sintomatologia psicotica al inicio o durante la evolucion, y se agrupan por patologias: errores congenitos del metabolismo, enfermedades geneticas, enfermedades autoinmunes e infecciosas, malformaciones del sistema nervioso central, epilepsia, patologia vascular, procesos reumatologicos, tumores cerebrales, y farmacos y sustancias psicoactivas. Se propone una pauta diagnostica en la que se valora la informacion obtenida a partir de la anamnesis y la exploracion y la aportacion de cada prueba diagnostica. Conclusiones. El numero de procesos que pueden manifestar sintomatologia psicotica a lo largo de su evolucion es muy elevado, y hay que considerar las claves que ofrecen la anamnesis y la exploracion. Esta revision puede ayudar a neuropediatras y otros especialistas a realizar una valoracion mas sistematizada de niños y adolescentes con cuadros psicoticos.

The lived experience of fathers whose children are diagnosed with a genetic disorder.

OBJECTIVE: To describe the father's experience of having a child diagnosed with a genetic disorder. DESIGN: Interpretive phenomenological analysis. SETTING: In-person interviews for participants living within 100 miles of the researcher; phone interviews with participants living more than 100 miles from the researcher. PARTICIPANTS: Six fathers of children diagnosed with genetic disorders. METHODS: Participants were recruited with the assistance of nurses, physicians, and genetic counselors. Snowball sampling, Internet and e-mail recruitment, and word of mouth were also used. Semistructured interviews were completed, audio recorded, and transcribed verbatim. RESULTS: Five themes emerged: the impact of diagnosis, seeking understanding, coping with effects of the disorder, looking to the future, and addressing a father's needs. CONCLUSION: Fathers of children diagnosed with genetic disorders described a lack of education and information regarding the diagnoses. They attributed this deficiency to a lack of knowledge among physicians, nurses, and other health care professionals. Coping with the effects of the disorder was identified as an integral part of adapting to meet the child's needs. Understanding the experience of a father whose child is diagnosed with a genetic disorder is necessary to ensure provision of proper intervention and care.

Trade-off between benefit and harm is crucial in health screening recommendations. Part II: evidence summaries.

Evidence on the effectiveness of health screening strategies may be direct (i.e., studies on screening vs. no screening) or indirect (i.e., studies that separately evaluate the screening test[s], the confirmatory test, or the treatment). Critical trade-offs in the balance between harm and benefit for many screening strategies mandate that advocates of health screening adhere to the ethical precepts of nonmaleficence, autonomy, confidentiality, and equity. In our first article, we pointed out five prerequisites to justifying a health screening program: (1) the burden of illness should be high, (2) the screening and confirmatory tests should be accurate, (3) early treatment (or prevention) must be more effective than late treatment, (4) the tests and the treatment(s) must be safe, and (5) the cost of the screening strategy must be commensurate with the potential benefit. As can be gleaned from these criteria, recommendations on screening must be tailored to specific populations. Recommendations in one country, no matter how authoritative, cannot be generalized to apply to all other countries. Although accuracy, effectiveness, and safety data may be global (criteria 2-4), burden of illness and efficiency (criteria 1 and 5) will always vary from country to country. Rather than review various national guidelines, in this last article of our two-part series, we present evidence summaries to illustrate health screening. Our examples were selected to address special issues related to four situations-screening for cancer, risk factors for disease, genetic disorders, and infectious diseases.

Assessment of psychosocial outcomes in genetic counseling research: an overview of available measurement scales.

The aim of the present paper was to describe and evaluate many of the measurement scales currently used in genetic counseling outcomes research. A team of three researchers reviewed the available literature and selected a variety of validated instruments suitable for measurement of genetic counseling outcomes. There are numerous scales to assess each of the following outcomes among counselees: satisfaction with genetic counseling; knowledge; decision-making; psychological adjustment; coping; perceived personal control; perceptions of disease risk; and family communication about genetic risk. However, the strengths and limitations inherent to each instrument warrant careful consideration prior to implementation. In the genetic counseling context, scale selection should be undertaken with thought directed towards the characteristics of the research sample (e.g. levels of literacy, culture, medical condition), the practicalities of the research setting (e.g. available funding and resources, time restrictions, researcher expertise), the purpose of the research (i.e. the specific aspect of the genetic counseling experience to be studied), and the science underlying the scale (e.g. theoretical framework, psychometric properties).

Parents' perceptions of functioning in families having a child with a genetic condition.

In a study of families having a child with a genetic condition, patterns of family functioning were identified through cluster analysis of families with two spouses. Patterns were based on both parents' assessments of family satisfaction and hardiness, as measured respectively by the Family APGAR and Family Hardiness Index. The validity and clinical significance of the clusters were supported by demonstrating that cluster membership distinguished between parental reports of their own quality of life and their child's functional status, as measured by the Quality of Life Index and the Functional Status II, respectively. The clusters were non-categorical in the sense that they did not depend on the type of genetic condition. These findings point to the importance of addressing family functioning as part of genetic counseling.

Design and psychometric evaluation of the Psychological Adaptation to Genetic Information Scale.

PURPOSE: To develop and psychometrically evaluate the Psychological Adaptation to Genetic Information Scale (PAGIS). DESIGN: A cross-sectional, Web-based survey of participants (n=323) recruited via Internet electronic mailing lists or Websites for people affected by genetic diseases. METHODS: Item analysis, confirmatory principal components analysis, and internal consistency reliability using Cronbach's alpha were used to construct the 26-item PAGIS. FINDINGS: Five factors (nonintrusiveness, support, self-worth, certainty, and self-efficacy) explained 57.7% of the variance in psychological adaptation to genetic information. The internal consistency reliability of the total PAGIS was .90, and the subscale reliabilities ranged from .77 to .87. CONCLUSIONS: Psychological adaptation to genetic information is a multidimensional phenomenon comprised of nonintrusiveness, support, self-worth, certainty, and self-efficacy. The PAGIS has initial reliability and validity for use in future research.

Disclosure, confidentiality, and families: experiences and attitudes of those with genetic versus nongenetic medical conditions.

Despite policy attention to medical privacy and patient confidentiality, little empirical work exists documenting and comparing experiences of persons with genetic versus nongenetic medical conditions concerning persons' disclosure to others as well as their views about appropriate confidentiality to and within families. The goal of this cross-sectional interview study with nearly 600 participants was to document and compare the experiences, attitudes, and beliefs of persons with strictly genetic conditions to those of persons with or at risk for other serious medical conditions in terms of the degree to which they have disclosed to others that they have the condition and their views about how others ought to maintain the confidentiality of that information. While almost all participants reported that family members knew about their condition, results suggest participants want to control that disclosure themselves and do not want doctors to disclose information to family members without their knowledge. Similarly, participants do not think family members should be able to get information about them without their knowledge but feel overwhelmingly that it is a person's responsibility to disclose information about hereditary conditions to other family members. Ambivalence about confidentiality was evident: while most participants did not mind doctors sharing information with other doctors when it was for their benefit, the majority also felt that doctors should be punished for releasing information without their permission. The views and experiences reported here generally did not differ by whether participants had genetic versus nongenetic conditions, suggesting that the extensive policy focus on genetic information may be unwarranted.

Goals, benefits, and outcomes of genetic counseling: client and genetic counselor assessment.

Most studies of outcomes of genetic counseling have focused on client knowledge, reproductive plans and behavior, or satisfaction. Other measures of the "value" of genetic counseling are needed to guide research assessing the impact of genetic counseling on individuals and populations, as well as to improve the process of providing care. To obtain input from providers, we conducted telephone interviews with six experienced genetic counselors, and then we held a focus group with 10 additional genetic counselors from a variety of practice settings. To obtain input from consumers, telephone interviews were also conducted with 19 past clients of these participating counselors. We found that counselor goals focus on meeting clients' needs, usually educating and providing psychosocial support. Clients often had few goals going into a session because they were unaware of what would be discussed or how the session would be structured. They usually did not expect to receive "counseling," and when they did, it was a welcome surprise. Both clients and counselors commented that a positive interpersonal interaction and "connecting" are primary measures of success. All clients appreciated the large amount of time spent with the counselor, and the manner (clear, comprehensive, and unhurried) of providing information. Many clients said that genetic counseling resulted in improved communication with their partners and other family members. Clients view the counselor as an "expert" and value the counselor as an on-going resource for both information and support. These "outcomes"f genetic counseling need to be assessed, and new measures must be developed.

The likely financial effects on individuals, industry and commerce of the use of genetic information.

In this paper I look at the financial implications of genetic testing, particularly in the employment and pensions fields. I have generally not covered life insurance, as that is covered in other papers in this Discussion Meeting. However, the issues are similar, although the emphasis is different. Inevitably there is an element of speculation involved; genetic testing is in its infancy and so we cannot predict either what information we will be able to obtain through genetic testing, nor the uses that may be devised for this information.

[A small-group center. A model trial for activities of a center for rare diseases and syndromes at the National Hospital]. / Smågruppesenteret. En modellutprøvning for Rikshospitalets utadrettede virksomhet for noen sjeldne sykdommer og syndromer.

The Centre for Rare Disorders at the National Hospital is a trial project in connection with the Government's Plan of Action for the disabled. The intention is to establish nationwide facilities which in cooperation with local resources can provide both medical, pedagogical and social services for persons with rare disorders and their families. The work at the centre is based on a life span perspective and the goal is improved coping, independence and better quality of life. The centre gathers, adapts and spreads information on 15 rare disorders. Representatives from the user organisations ensure that the users have a strong influence on the management of the centre. It is hoped that systematic evaluation of the centre's activities will give an answer to the Government and to the host hospital as to whether the intentions and goals will be fulfilled or not during the project period.