Laura Forrest

Communicating genetic information in families – a review of guidelines and position papers

This article aims to review ethical and clinical guidelines and policies addressing the communication of genetic information in families. Websites of national and regional bioethics committees, national human genetics societies, international health organisations, genetic interest groups and legal recommendations committees were searched for guidelines and policies. The databases Medline, Web of Science and Google Scholar were also utilised to search for additional guidelines relating to the communication of genetic information in families. The guidelines and policies included in this review are limited to those available in English. The search resulted in guidelines from 18 international, regional and national organisations from six countries pertaining to family communication of genetic information. The following ideals were common in their guidelines: (1) individuals have a moral obligation to communicate genetic information to their family members; (2) genetic health professionals should encourage individuals to communicate this information to their family members; and (3) genetic health professionals should support individuals throughout the communication process. The difference between the organisations guidelines was the inclusion of information about the role of the health professional in supporting clients during the process of communicating genetic information to their family members. Only two recommendations suggested that the health professional should support their clients by identifying at-risk family members, but more guidelines recommended that directive counselling should be undertaken to encourage clients to communicate genetic information to their family members. In conclusion, the guidelines provide an overview of the role that genetic health professionals may undertake; however, there are gaps that need to be addressed.

Health first, genetics second: exploring families' experiences of communicating genetic information

Genetic information may have health and reproductive implications for the proband and their family members. The responsibility for communicating this information within families generally lies with the proband or consultand. Previous research has explored the barriers and facilitators to communication, particularly in families affected with familial cancer syndromes. This study is an exploration of families experiences, which aims to elucidate the process of communicating genetic information in families affected with non-cancer genetic conditions. The methodology involved 12 semi-structured interviews with probands, consultands and their family members. There were six different genetic conditions present in the families: adrenoleukodystrophy (n=3), cystic fibrosis (n=3), fragile X syndrome (n=1), haemochromatosis (n=1), balanced reciprocal chromosomal translocation (n=3) and Robertsonian chromosomal translocation (n=1). The results presented arise from two key themes, (1) the diagnosis and (2) post diagnosis. The interview data illustrate that the time of the diagnosis is a traumatic experience for families and that communication stimulated by this event revolves around informing family members about the diagnosis, but not warning them of their genetic risk. Post diagnosis, the collection of information about the genetic condition and continued communication to more distant family members, often using pre-existing family communication patterns, enables the continuation of communication about the genetic condition.

Population-based carrier screening for cystic fibrosis: a systematic review of 23 years of research

Cystic fibrosis is the most common severe autosomal recessive disease, with a prevalence of 1 in 2,500–3,500 live births and a carrier frequency of 1 in 25 among Northern Europeans. Population-based carrier screening for cystic fibrosis has been possible since CFTR, the disease-causing gene, was identified in 1989. This review provides a systematic evaluation of the literature from the past 23 years on population-based carrier screening for cystic fibrosis, focusing on the following: uptake of testing; how to offer screening; attitudes, opinions, and knowledge; factors influencing decision making; and follow-up after screening. Recommendations are given for the implementation and evaluation of future carrier-screening programs.Genet Med 2014:16(3):207–216

Genetic health professionals and the communication of genetic information in families: Practice during and after a genetic consultation†

The communication of genetic information in families is an important process which can inform family members that they are at risk. However, evidence suggests that at‐risk family members are often uninformed. Genetic health professionals have a role to assist consultands to communicate genetic information to their family members. Therefore, the aim of this study was to investigate genetic health professionals practice with regard to the familial implications of a genetic diagnosis and subsequent family communication. An online survey resulted in 626 responses from genetic health professionals internationally. The results indicated that over 90% of genetic health professionals consistently counsel consultands about the familial implications of a genetic diagnosis during a consultation. Also there were no major differences in practice between clinical geneticists and genetic counselors. An average of 79% of genetic health professionals always send a summary letter to the consultand after a consultation. In contrast, 41% of genetic health professionals never write letters for at‐risk family members. Other support is available to consultands after a consultation, but the availability of support relies on consultands and family members acting proactively and seeking out assistance from genetic health professionals for family communication. This may result in family members who are unaware that they are at risk of carrying and/or developing a genetic condition. This study is limited by the self‐selection and self‐reporting of the respondents practice.

An audit of clinical service examining the uptake of genetic testing by at-risk family members

Purpose:The aim of this study was to investigate the uptake of genetic testing by at-risk family members for four genetic conditions: chromosomal translocations, fragile X syndrome, Huntington disease, and spinal muscular atrophy.Methods:A clinical audit was undertaken using genetics files from Genetic Health Services Victoria. Data were extracted from the files regarding the number of at-risk family members and the proportion tested. Information was also collected about whether discussion of at-risk family members and family communication during the genetic consultation was recorded.Results:The proportion of at-risk family members who had genetic testing ranged from 11% to 18%. First-degree family members were most frequently tested and the proportion of testing decreased by degree of relatedness to the proband. Smaller families were significantly more likely to have genetic testing for all conditions except Huntington disease. Female at-risk family members were significantly more likely to have testing for fragile X syndrome.Conclusion:The majority of at-risk family members do not have genetic testing. Family communication is likely to influence the uptake of genetic testing by at-risk family members and therefore it is important that families are supported while communicating to ensure that at-risk family members are able to make informed decisions about genetic testing.Genet Med 2012:14(1):122–128

Clinically Significant Germline Mutations in Cancer-Causing Genes Identified Through Research Studies Should Be Offered to Research Participants by Genetic Counselors

Genetic sequencing, resulting in the identification of pathogenic germline mutations conferring significantly increased cancer risk, has become de rigueur for research studies with access to populations with and without personal and family histories of cancer. Genetic technology is now more efficient and affordable, and evidence has amassed of the pathogenicity of identified gene mutations. Debate continues about the benefits and harms of returning research results. Benefits include the clinical and personal utility of the genetic information and the potential for treatment or prevention. An example is cancer genetics, where efficacious cancer risk-management strategies known to reduce cancer-related morbidity and mortality are available to individuals who carry a high-risk germline mutation. Harms include psychological distress, perceived patient discrimination and stigmatization, and erroneous results as a result of research laboratories’ not being required to adhere to the Clinical Laboratory Improvement Amendments standards and regulations. The notion of “therapeutic misconception” has also been cited as a risk to participants. This theory describes participants’misunderstanding about the boundaries between research and clinical domains, where participants assume that a research study will provide clinical benefit. Current opinion proposes that researchers have an ethical duty to return individual genetic research results subject to the existence of proof of validity, significance, and benefit. Therefore, attention needs to be focused on how the information should be communicated so participants can make an informed decision about whether they wish to receive their genetic research results. Australia offers a valuable perspective on this issue because of the evolving methods used to return results and the availability of data regarding participants’ experiences and actions. The predominant method of notification in Australia has involved sending consenting participants a letter informing them that genetic information has been identified by the research study. Participants who wished to act upon the letter could contact a familial cancer center (FCC) for genetic counseling and potential confirmation through clinical genetic testing. Australian FCCs are funded by the health system, theoretically making them more readily accessible to research participants. This method was purposefully chosen as a sensitive way to approach participants and breaking to them what was often unexpected news and to optimize their independent decision making about whether to pursue their genetic information. Furthermore, participants’ privacy was maintained by not being contacted directly by the research team, and this lack of contact also reduced the capacity for therapeutic misconception. The content of the notification letters tended to be fairly uniform across different studies, with each study contextualizing the letter according to the inherited cancer syndrome under examination. However, as exploratory qualitative research findings emerged that demonstrated chiefly that participants did not understand or value the letter, the strength and clarity of the wording in the letter has increased. The wording has changed from “the research has identified information that may have relevance for you and your family” to “our research has identified information relevant to your family. This means a genetic change has been found in your family which may account for the family’s experience of cancer” (Australian Ovarian Cancer Study [AOCS] notification letter, October 2007). The uptake rate of confirmatory genetic testing postnotification offers one perspective of examining outcomes resulting from sending these notification letters to participants. Four Australian studies have published uptake rates of confirmatory genetic testing by participants who have received a notification letter. In three of these studies—the Australian Breast Cancer Family Study, the Kathleen Cuningham Foundation Consortium for Research into Familial Aspects of Breast Cancer, and the AOCS—the percentage of participants who received a notification letter and had confirmatory genetic testing ranged from 8% to 49%. Slightly more participants (56%) enrolled in the Australian site of the multinational Colon Cancer Family Registry (CFR) confirmed their mismatch-repair-gene mutation status through confirmatory genetic testing. A consistent outcome of notifying participants by letter of the availability of genetic information, regardless of the wording, is that, in most Australian studies, more than half of the participants did not act upon the letter. It was unknown whether these

Connecting patients, researchers and clinical genetics services: the experiences of participants in the Australian Ovarian Cancer Study (AOCS).

Population-based genetic research may produce information that has clinical implications for participants and their family. Researchers notify participants or their next of kin (NoK) about the availability of genetic information via a notification letter; however, many subsequently do not contact a family cancer centre (FCC) to clarify their genetic status. Therefore, the purpose of this study was to examine research participants’ experience of receiving a notification letter and the factors that influenced contact with an FCC. Twenty-five semi-structured interviews were conducted with research participants (n=10) or their NoK (n=15) who had received a notification letter following participation in the Australian Ovarian Cancer Study. There were a number of factors which impacted participants’ access to genetic counselling at an FCC. Some participants had unmet information and support needs, which were addressed by their participation in this psychosocial interview study. Recruitment and participation in this study therefore inadvertently increased a number of participants’ intention to contact an FCC. For others, participation in this study facilitated access to an FCC. Recommendations are proposed regarding future notification as well as implications for clinical practice. An approach that also provides opportunity to address research participants’ support and informational needs before contacting a clinical genetics service as well as practical guidance for accessing genetic services would facilitate timely and smooth access for research participants who are interested in following up clinically relevant genetic test results.

Making Sense of SNPs: Women’s Understanding and Experiences of Receiving a Personalized Profile of Their Breast Cancer Risks

Genome wide association studies have identified a number of common genetic variants - single nucleotide polymorphisms (SNPs) – that combine to increase breast cancer risk. SNP profiling may enhance the accuracy of risk assessment and provides a personalized risk estimate. SNP testing for breast cancer risks may supplement other genetic tests in the future, however, before it can be implemented in the clinic we need to know how it will be perceived and received. Semi-structured qualitative interviews were conducted with 39 women who had previously had a breast cancer diagnosis and undergone BRCA1/2 testing, participated in the Variants in Practice (ViP) study and received personalized risk (SNP) profiles. Interviews explored their understanding and experiences of receiving this SNP information. Women reported feeling positive about receiving their personalized risk profile, because it: provided an explanation for their previous diagnosis of cancer, vindicated previous risk management decisions and clarified their own and other family members’ risks. A small group was initially shocked to learn of the increased risk of a second primary breast cancer. This study suggests that the provision of personalized risk information about breast cancer generated by SNP profiling is understood and well received. However, a model of genetic counseling that incorporates monogenic and polygenic genetic information will need to be developed prior to clinical implementation.

The impact of participation in genetic research for families with cleft lip with and without cleft palate: a qualitative study.

Despite being the most common congenital facial anomaly, little is understood about the genetic contribution to isolated clefts of the lip with or without cleft palate (CL/P). ‘OzCleft’, a family-based genotype/phenotype study, is investigating this further. Participation for families involves various clinical investigations of the child with the cleft, and their unaffected sibling(s) and parents. Informal feedback from individuals involved in OzCleft suggested that participation in this research programme had benefits for families. Taking a qualitative approach, this study sought to investigate this hypothesis further. Semi-structured in-depth interviews were conducted with nine parents who had participated in OzCleft. All parents described participation as a positive experience for themselves and their families. Perceived benefits included a greater appreciation of the cleft treatment experience by unaffected family members. Being involved in a genetic study raised issues for parents regarding the cause of clefting in their child. While some parents found the possibility of a genetic component reassuring, it also raised questions about the potential implications for future generations. Parents were largely unsure about how to communicate this information to their children and the predictive value of this information. This study suggests a lack of genetic understanding and/or perceived value of genetic information by parents of children with CL/P that, in turn, highlights the need for increased support from genetic health professionals in this area.

Are “part-time” general practitioners workforce idlers or committed professionals?

BackgroundThe traditional view of general practice holds that only general practitioners (GPs) in full-time clinical practice can provide quality patient care. Nevertheless, increasing numbers of GPs are choosing to work sessionally, that is, ostensibly “part-time”. There are concerns about the health workforce’s ability to meet demand and also fears that patient care may be compromised. We sought answers to a) what activities do GPs undertake when not consulting patients, b) why do they choose to work sessionally, and c) does sessional general practice reflect a lack of commitment to patients and the profession?MethodsSemi-structured interviews were conducted with GPs who worked sessionally, (i.e. six or fewer sessions a week in clinical general practice, where a session comprises four consecutive hours of patient care). These data were analysed qualitatively and saturation was reached.ResultsThe majority of participants were in full-time paid employment, while part-time in clinical general practice. They reported that consultations increasingly required the management of patients with complex, chronic conditions who also required psychological management. Coupled with unrealistic patient expectations, these factors led GPs to be concerned about maintaining the quality patient care they considered professionally desirable. Many diversified their work activities to ensure that they retained their professional standards.Conclusion“Part-time” general practice is a misnomer that masks the contribution these GPs make as part of the health workforce. Sessional practice more accurately describes the nature of our participants’ clinical work. Their choice of sessional work is a professional response to the increasing demands within the consultation. It enables GPs to maintain their commitment to quality patient care and their profession, while attenuating the challenges of demanding consultations. Sessional general practitioners demonstrate strong commitment to their patients and the profession.