ABSTRACT Cystic fibrosis (CF) is an autosomal recessive disorder that occurs in all ethnic groups. Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene are responsible for pulmonary obstruction, chronic lung infections, pancreatic insufficiency, meconium ileus, failure to thrive and infertility. Genetic testing for CF at the DNA level is available. A diagnosis of CF in an individual has implications for other family members and so genetic counselling should form part of CF management. Genetic counselling has been offered by the Clinical Unit of the Division of Human Genetics, National Health Laboratory Service and the University of the Witwatersrand, Johannesburg, for many years. At the beginning of 2006, genetic services were introduced into the CF Clinics of Johannesburg Hospital by way of specialist Genetic Counselling Clinics. The study aimed to determine who utilises the CF genetic counselling services and why, to estimate the number of at-risk relatives per family, and how many of them had mutation testing and genetic counselling. Finally, the study explored what impact the specialist Genetic Counselling Clinics had on the overall service of genetic counselling. The files of 153 families seen for CF genetic counselling from 1990 to 2006 were analysed. The majority of counsellees (93%) were white. Most counsellees were parents of CF probands (35%). Relatives with carrier risks of 67% (siblings) and 50% formed only 7% and 6% of all counsellees respectively. Most individuals attended genetic counselling in order to gather information. On average, 5.9 ± 3.45 families were seen for CF genetic counselling per year from 1990 to 2005, whereas in 2006, 58 families were seen. Paediatrician, physician and nurse referrals increased notably during 2006 compared to prior years. In 140 unrelated CF-affected families, 1991 at-risk relatives, with carrier risks above 25%, were identified. Only 11% of these relatives had mutation testing and only 8% attended genetic counselling. Uptake of genetic counselling is greater when the service is integrated into CF treatment clinics than when it is offered externally. The low uptake of mutation testing and genetic counselling by at-risk relatives suggests that new methods of educating individuals for cascade screening and testing are required.

No description available.

Thesis (Ph. D.)--University of New South Wales, 2002. / Also available online.

Student number: 0200150A MSc (Med) Genetic Counselling - School of Pathology / Increasing numbers of pregnant women of advanced maternal age (AMA) counselled in the prenatal genetic counselling clinics in Johannesburg are human immunodeficiency virus (HIV) positive. This has altered the information these women must consider when deciding about amniocentesis for prenatal diagnosis of chromosomal abnormalities. Antiretroviral treatment (ART) is advised for HIV positive women prior to the procedure, to minimise vertical transmission from mother to child. The risk of mother to child transmission (MTCT) of HIV also necessitates counselling regarding termination of pregnancy (TOP). A study over two 6-month periods in 2003 and 2004 documented the HIV status of the advanced maternal age women attending genetic counselling clinics at three academic hospitals in Johannesburg, and the choices these women made regarding testing for possible chromosome abnormalities. An interview schedule, conducted over 6 months in 2004, investigated the HIV positive women’s perceptions of HIV in pregnancy, and their thoughts on termination of pregnancy based on HIV transmission risk. Of 169 women seen over six months, February to July 2003, 83 (49%) were HIV negative, 15 (9%) were HIV positive and 71 (42%) were of unknown status. Forty (48%) HIV negative patients had amniocenteses compared to 2 (13%) HIV positive women. In 2004, 181 patients were seen; 100 (55%) were HIV negative, 29 (16%) were HIV positive and 52 (29%) were of unknown status. Thirty-nine (39%) HIV negative patients had amniocenteses compared to 4 (14%) HIV positive women. Data from fifteen completed questionnaires indicated that most women understood the severity of HIV infection, 12/15 (80%), five (33%) considered termination of pregnancy based on the HIV transmission risk, and four (27%) would have had amniocentesis if they had been HIV negative. A significant percentage of AMA women attending the genetic counselling clinics are HIV positive, and they are faced with difficult issues, including the risk of chromosome abnormalities in the fetus, the risk of transmission of HIV during pregnancy and amniocentesis, and the option of TOP up to 20 weeks gestation based on the risk of vertical HIV transmission. It is vital that cogent policies are developed to provide optimum care for these women. Ideally, the access to highly active antiretroviral therapy (HAART) throughout pregnancy, to reduce the risk of MTCT of HIV to about 1%, would make the option of prenatal diagnosis a safer one for AMA women to consider.

For this project I describe the socio-historical development of a particular application of genetic prenatal diagnosis, in terms of changing social relations that govern an ethics of reproductive choice. I examine ways that medicine and government articulate prenatal diagnosis to problematise the maternal body and govern women's reproductive choices about chromosomal abnormality in the fetus. Since its introduction in the early 1970s, the major use of prenatal diagnosis has been to detect chromosomal abnormalities-in particular, Down syndrome-in the fetus. Medico-scientific knowledge claims negotiated in everyday practices in the genetic counselling clinic between health professionals and their clients are situated within broader social relations. Negotiations between medicine and government have produced technoscientific possibilities, realised with greater or lesser success in the co-construction of a workable prenatal diagnosis standardised package. I describe how these socio-technical relations have produced similarities and differences across time, and national and professional boundaries. My analysis draws on observations in three genetic counselling clinics, and of the health professionals' other work activities. I also draw on interviews with them and other actors in that arena, as well as claims made about prenatal diagnosis technologies in the medico-scientific literature. I analyse my data using concepts developed in social worlds/arenas theory within a Foucauldian framework of social relations that govern the body. Since the early formation of a standardised package of genetic counselling about amniocentesis, ethical decisions about prenatal diagnosis have identified multiple parts of the self to be governed. This ethics has relied on a duty to make genetically responsible decisions as a particular way to relate to oneself, although it has been expressed in different ways. Newer technologies have articulated greater ethical possibilities for governing the self by co-constructing new ways of assembling the constituent components. Throughout, there have been tensions between two major aims for governing the self: that of giving birth to a healthy baby, and that of managing maternal rationality in order to act as an autonomous rational individual. I have thus described how a woman's use of prenatal diagnosis is not simply one of individual choice. Her decision is a complex ethical one that is historically and socially contingent on relations between medicine and government that present the maternal body in certain ways for her to act upon herself.

Schizophrenia is a genetically complex neuropsychiatric disease. Myths and uncertainty about aetiology, and concerns about familial recurrence, may contribute to the significant stigma and burden on families. There has recently been concrete progress in understanding individual genetic causes of schizophrenia, which are now known to extend beyond 22q11.2 microdeletions to include other large rare copy number variations. However, there are limited data on issues germane to the translation of these genetic discoveries into clinical practice. The aim of this thesis was to evaluate the contemporary clinical applicability of genetic testing and genetic counselling in schizophrenia. First, general genetic counselling was provided to both adults with schizophrenia without individually relevant genetic test results and their family members. Pre-counselling, there was evidence of widespread misconceptions about schizophrenia aetiology and familial recurrence risks, which were associated with considerable psychological distress. Post-counselling, the myriad significant lasting benefits of genetic counselling included reductions in stigma. The results provided initial evidence of need for, and efficacy of, genetic counselling for schizophrenia. A first ever study was then conducted of the impact of providing a specific aetiological explanation for schizophrenia. Affected individuals and family members were found to value a molecular genetic diagnosis of a 22q11.2 microdeletion for its ability to explain the presence of stigmatized neuropsychiatric conditions. An investigation of transmission patterns and reproductive fitness associated with 22q11.2 microdeletions provided novel insights into the evolutionary biology and clinical correlates of this structural rearrangement. The results demonstrated the scientific and clinical benefits of identifying a genetic subtype of schizophrenia. Last, high resolution genome-wide microarrays were used to investigate rare copy number variations in a prospectively recruited community-based schizophrenia cohort. Clinically significant variants were greatly enriched in schizophrenia, even with 22q11.2 microdeletions a priori excluded. The collective prevalence of these genetic variants in a single community catchment area was high, approaching that seen in autism, where clinical microarray testing is now a first-tier diagnostic test. Collectively, the findings of these pioneering studies suggest a role for genetic testing and genetic counselling in the contemporary management of schizophrenia.

Schizophrenia is a genetically complex neuropsychiatric disease. Myths and uncertainty about aetiology, and concerns about familial recurrence, may contribute to the significant stigma and burden on families. There has recently been concrete progress in understanding individual genetic causes of schizophrenia, which are now known to extend beyond 22q11.2 microdeletions to include other large rare copy number variations. However, there are limited data on issues germane to the translation of these genetic discoveries into clinical practice. The aim of this thesis was to evaluate the contemporary clinical applicability of genetic testing and genetic counselling in schizophrenia. First, general genetic counselling was provided to both adults with schizophrenia without individually relevant genetic test results and their family members. Pre-counselling, there was evidence of widespread misconceptions about schizophrenia aetiology and familial recurrence risks, which were associated with considerable psychological distress. Post-counselling, the myriad significant lasting benefits of genetic counselling included reductions in stigma. The results provided initial evidence of need for, and efficacy of, genetic counselling for schizophrenia. A first ever study was then conducted of the impact of providing a specific aetiological explanation for schizophrenia. Affected individuals and family members were found to value a molecular genetic diagnosis of a 22q11.2 microdeletion for its ability to explain the presence of stigmatized neuropsychiatric conditions. An investigation of transmission patterns and reproductive fitness associated with 22q11.2 microdeletions provided novel insights into the evolutionary biology and clinical correlates of this structural rearrangement. The results demonstrated the scientific and clinical benefits of identifying a genetic subtype of schizophrenia. Last, high resolution genome-wide microarrays were used to investigate rare copy number variations in a prospectively recruited community-based schizophrenia cohort. Clinically significant variants were greatly enriched in schizophrenia, even with 22q11.2 microdeletions a priori excluded. The collective prevalence of these genetic variants in a single community catchment area was high, approaching that seen in autism, where clinical microarray testing is now a first-tier diagnostic test. Collectively, the findings of these pioneering studies suggest a role for genetic testing and genetic counselling in the contemporary management of schizophrenia.

Background: Presymptomatic genetic testing should always involve a considered choice. Young adults are at a key life stage as they may be developing a career, forming partnerships and potentially becoming parents. Presymptomatic testing may therefore affect the future lives of consultands significantly when testing is undertaken in early adulthood. Aim: To explore presymptomatic testing for hereditary cancer in consultands aged 18-30 years with particular reference to psychosocial impact, the decision-making process and the consequent counselling needs. Methods: A mixed-methods sequential exploratory design was used, comprising a systematic review, a qualitative study and a quantitative study. Results of all phases were used to build a theoretical model regarding the process of presymptomatic testing in young adults. Findings: The systematic review indicated that many participants grew-up with little or no information concerning their genetic risk. The experience of genetic counselling was either reported as an opportunity for discussing problems or associated with feelings of disempowerment. Parents appeared to have exerted pressure on their children during the decision-making process. However, as a result of the qualitative study, the influence of other people and the decision-making process prior to counselling were identified as key factors. Further results from the quantitative phase underlined that parents felt they had control over the decisions their children made, while the majority of the young adults reported the request for the genetic test as their own decision. A new theoretical model of decision making and impact on young adults was built to synthesise the overarching experience of participants in this research project. Conclusion: Counselling approaches to this population may require modification both for young adults and their parents. Young adults may benefit from a multi-step approach to presymptomatic testing. Parents need to be more informed that genetic counselling is a forum where information can be obtained and young adults can talk about the testing decision, regardless of whether they want to be tested or not. The traditional ‘wait until they come to us’ approach by health services may be failing to meet the educational and emotional needs of this population.

Yes / Currently there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, first, that family networks hold strong potential for cascading genetic information, making the adoption of a family centred approach an efficient strategy for this community. However, this is dependent on provision of high quality and timely information from health care providers. Secondly, families’ experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals’ views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information. / Department of Health

The effect of psychosocial information resources on the psychological impact of genetic testing for patients Background: The genetic testing process has been shown to have a profound psychosocial impact on patients and families, yet research suggests that there is a lack of practical and helpful psychosocial information written to support decision-making. Ideally, this should be available for use both before and after genetic testing and should be easily accessed through genetic clinics. The development of pre-written leaflets or on-line resources which draw on the experiences and advice of families who have been through similar experiences, and are readily available through genetic clinics, might be one way of helping families make necessary adjustments. Aim: The aim of this study was to develop information resources for a) people undergoing carrier testing, and b) parents of children with undiagnosed conditions, and to pilot the use of these resources with service users. Methods: A systematic literature review was conducted to identify key themes to inform the content of the resources. To build on these findings, in-depth interviews were conducted with 11 people who had undergone carrier testing and 14 parents of children without a diagnosis. Interview data were analysed using the grounded theory method. A grey literature search of existing patient information was also conducted. These three phases informed the content of information resources. The development process also included input from genetic specialists, patient group representatives and interviewees. Finally, a pilot study was conducted through three genetic centres to assess the feasibility of a study testing the use of the resources. Findings: The participants in this study were striving for empowerment: carriers sought reproductive empowerment; parents developed empowerment strategies in order to advocate for their child. Moreover, a theory named ‘reconstructing the meaning of being a parent’ was constructed to describe the experience of parenting a child for whom no clear care pathway existed. The importance of providing timely information was identified as being a key factor in supporting parents during their search for a diagnosis. A new model was built to summarise the overarching experience of participants in this study. Conclusions: Empowerment was identified as a dynamic and multi-faceted construct. Health professionals and support groups can help facilitate the empowerment process through the provision of timely psychosocial information. This is particularly important in an age when patients are expected to take greater control than ever before over decisions affecting their healthcare.