Breast cancer is the most common malignancy affecting females globally. Hereditary breast and ovarian cancer (HBOC) syndrome is caused by pathogenic variants in BRCA1 and BRCA2 and is seen in approximately 50% of families with a strong history of breast and ovarian cancers. Predictive testing (PT) is offered to unaffected individuals with a positive family history of HBOC, with an already identified BRCA1 or BRCA2 mutation in an affected family member. There is an overwhelming amount of research that has focused on the after-effects of diagnostic genetic testing for HBOC but there has been little investigation into how individuals experience the actual PT process. The present study therefore aimed to investigate individuals’ decisions for undergoing and their experiences of PT for HBOC in a local context, by focusing on at-risk South African individuals residing in the Western Cape Province. Sixteen participants were recruited retrospectively from the breast cancer and/or clinical genetics clinics at Groote Schuur Hospital, Tygerberg Hospital and private genetic counselling practices in Cape Town. Semi structured interviews were conducted, and the interview transcripts were analysed using the framework approach for qualitative data analysis. Using this approach, five themes were identified relating to the perspectives and experiences of individuals undergoing PT for HBOC, in selected settings in the Western Cape. While some participants felt that their decision to pursue PT was influenced by their family history of cancer and the associated cancer-related distress, others felt that their decision was made out of a sense of duty to their families or in solidarity with those that were affected or received a positive test result. Overall, the participants felt that the pre-test counselling was beneficial in allowing for an improved understanding of HBOC, however not all participants felt that the pre-test counselling prepared them for receiving their results. Receiving a negative test result was often accompanied by feelings of guilt and did not exempt participants from the fear of developing cancer. Some of the concerns raised by participants that received a positive test result were centred around prophylactic intervention and its effect on body image. Overall, participants felt empowered by their mutation status and felt that they were better able to manage their risk. The need for additional support, both practical and emotional support, was particularly evident amongst mutation-carriers. The findings of this study provide valuable insight into the perspectives and experiences of this population, which could potentially impact the services that are provided to individuals undergoing PT for HBOC in similar settings.

Congenital hearing loss (HL) occurs in 1-2 per 1000 newborns globally. Of all the congenital diseases that occur worldwide, HL remains the most disabling, with the highest rate for age-standardised disability life years and is a significant public health concern particularly in the developing world. In South Africa, 6 in 1000 newborns, have disabling HL. Genetic aetiology accounts for half of the cases of prelingual HL and of these 70% are nonsyndromic. There is ongoing research into the genetic basis of HL in the South African setting as at present, genetic testing for HL is largely uninformative in most African populations. Previous studies have examined the psychosocial challenges experienced by parents related to their child's HL, but in South Africa there have been no studies investigating the hereditary aspects of HL and how they may be related to the experiences of parents. Furthermore, the understanding and comprehension of genetics concepts is unknown in this population and needs to be explored before appropriate genetic counselling may be provided to parents of children with hereditary HL. Therefore, the aim of this research was to examine the perspectives, experiences and understanding of parents, whose children are deaf, potentially due to a nonsyndromic genetic aetiology, in a selected setting in Cape Town. Eleven participants were recruited through the clinical genetics service at Red Cross War Memorial Children's Hospital and the Dominican School for Deaf Children in Cape Town. Semi-structured interviews were conducted, and the transcripts analysed using the framework approach for data analysis. Through this approach, five themes were identified relating to the experience of parenting a deaf child, parents' understanding of the cause of their child's HL and the way that their child's difference or normalcy is perceived. Most parents were unable to identify the cause of their child's HL unless there were previous cases of HL in the family, but almost all were interested in pursuing genetic testing to assist them in finding answers. The time from the diagnosis had been an emotional and confusing time for many of the participants, who found means to cope and adapt to their child's HL through faith and support systems. Each of the participants had a unique experience with regards to their child's HL, some needing to make sacrifices and overcome practical challenges in order to provide for their child. Participants both rejected shame and pity with regards to their child's HL and embraced that their child was different, part of the Deaf world, but that this difference does not define them. This research could influence the genetics services provided for this population. It is imperative to understand the experiences and comprehension of this population so that improvements can be made to provide appropriate services.

Includes bibliographical references. / The aim of this study was to explore possible factors that may affect non-adherence and adherence to surveillance guidelines for mutation positive individuals who are at high risk of developing CRC in the areas of the Northern Cape of South Africa. The study took place in rural, impoverished areas of the Northern Cape of South Africa and used a qualitative, exploratory research design to prospectively study the participants.

Includes bibliographical references / The burgeoning knowledge in genetics implies that genetic services (including clinical and counselling) will be in increasing demand in the future. This study investigated South African doctors' genetic education, knowledge and attitudes towards genetic services and examined whether these factors affect referral to genetic services. Several studies have indicated that health professionals have poor understanding of genetics and genetic conditions, and this lack of insight extends to knowledge of genetic services and how and when to access them, so that those who would benefit from services might not gain access to them because they are not referred by their doctors (Delikurt et al., 2015). METHODS: A questionnaire was developed based on published research and questions relating to the aims of the project. Forty-one questions were asked, covering referral patterns, demographics, education, knowledge and attitudes to genetic services and genetic counselling. The sample population consisted of 140 GPs attending a family practitioners' conference. Fifty-one responses were received. Results were analysed using descriptive statistics and content analysis of open-ended questions. RESULTS: Results show that 52.9% of general practitioners have referred to genetics in the past, 92.2% think they will refer in future and only 49% know how to access genetic services. Doctors who knew how to access genetic services were more likely to have previously referred patients to these services. Almost half the doctors who had not used genetic services previously felt that genetic services were difficult to access and several attributed this to their lack of knowledge. Doctors who had the most education were more likely to have previously referred patients to genetic services. Doctors indicated that they would like more education on basic genetics, common genetic conditions and genetic services via forums such as conferences, CME activities and online resources. More than half of the doctors rated themselves as "not confident" in their genetic knowledge. Down syndrome was the most commonly seen genetic condition in practice, followed by cystic fibrosis and breast cancer. More than 80% of respondents did not know about direct-to-consumer testing, but 46% thought they might be approached to interpret the results of a direct-to-consumer test in future. Doctors showed poor understanding of the ethics of testing minors for genetic conditions. Genetic services and genetic counselling were seen as indispensable by 66.7% and 74.5% of doctors respectively. CONCLUSIONS: Overall, doctors' knowledge of genetics seems poor and most of them indicate they would like more education on basic genetic concepts, referral guidelines for genetic services and how to access genetic services, which agrees with the amount of education being the most important factor relating to previous referral to genetic services. This study will provide guidance for awareness and education programmes, and inform the future development of genetic services in South Africa.

This study explored the experiences of individuals within the clinical genetic service in South Africa, with inherited retinal disease. Methods: This qualitative research was based on a grounded theory approach. Semi-structured interviews were carried out after obtaining approval from the University of Cape Town Research and Ethics committees as well as from study participants themselves. Ten willing individuals were interviewed using an open-ended question guide to extract information about their experiences with vision loss including but not exclusively, concerning participants knowledge about their condition, ability to make decisions and their adaptation experiences. Interviews were audio recorded, transcribed verbatim and a reiterative thematic analysis performed on the raw data. Results: A range of themes and sub-themes emerged from the data that marked participants' experiences from the time of onset of vision loss. The main broad themes include "a roller coaster journey," "learning how to survive," "a genetic condition affecting the back of the eye, and "paving the way forward." Conclusions: The four themes presented in an almost linear fashion, marking a journey patients experienced from the onset of symptoms to the time of the interview. The initial stage of their journey was marked by difficulties and challenges exacerbated by the psychopathological responses reported in this dissertation. This stage was perceived to be prolonged and often extended into adulthood. The messages from the data support a view that the diverse and extended nature of this initial period was due to the limited support this group of participants received from the low vision specialists they consulted with. A significant impression of frustration and disillusionment was experienced by participants on not receiving information and guidance from these health care providers. Various mechanisms of support and control positively influenced patients' learning how to cope and survive their journey with visual impairment. Coping, learning what their condition is, what the causes are and the risks involved for future generations, empowered the participants in this study to obtain a view of a future for themselves and to make relevant decisions and choices necessary to realise the way ahead. Taken together though, continued education was deemed worthwhile.

Preimplantation genetic diagnosis (PGD) is an alternative reproductive technology integrated with in-vitro fertilisation (IVF). It is a well-established technique offering reproductive options for families at a high risk of transmitting a genetic disorder, allowing them to avoid a termination of pregnancy (TOP). Consanguineous unions are common and encouraged in many Arab communities. This can lead to an increased risk of one or more autosomal recessive disorders that may occur within the family. Traditional prenatal testing involves testing fetal cells with the option of TOP of an affected fetus. In Arab communities where TOP is restricted under Muslim law, such testing is not acceptable. For these couples and their family members, PGD is a feasible option as the fetus is diagnosed before implantation and allows for only healthy embryos to be implanted. However, undergoing PGD is relatively new in the Arabic Muslim countries and Omani patients have only recently had access to the service. This study utilised a phenomenological approach to explore the experience of Omani families who had selected to undergo PGD as a means of reducing the risk of having a child affected with a genetic disorder. Fourteen participants from eight families who underwent PGD were interviewed. Data collected were analysed using thematic analysis. The research identified five main themes; Desire for a Healthy Child; Anxiety "Taraqub"; Unforeseen; Secrecy; Me and My Partner. The PGD experience was reported as physically and emotionally distressing. Some participants felt attached to their embryos regardless of health status, while the majority did not anticipate the loss of intimacy, autonomy and control they experienced, particularly related to the insemination process. The social and religious background of participants played a significant role in the participant's perception of PGD, which has both practical and psychosocial implications. The findings of the research have provided insight into the PGD experiences of Omani families and can be used to improve the services that are currently available to these families.

Background: Precision Medicine (PM) is a model whose goal is to tailor healthcare to meet the individual patient’s treatment and management needs. Precision Management of Epilepsy in South African Children (PME) is an on-going study at the University of Cape Town (UCT) gathering preliminary insight into the potential of PM initiatives which include remote monitoring with a wearable device, a phone app and a genetic and pharmacogenomics study in a South African setting. Feasibility and acceptability of new innovations is dependent on caregivers. This sub-study aims to better understand the caregivers’ experiences, perceptions and expectations of the PME initiatives. Methods: Ethical approval was obtained from UCT for this qualitative sub-study (HREC 775/2018). Twelve participants were purposively recruited from a cohort of 40 caregivers of children with refractory epilepsy recruited for the PME study attending Red Cross War Memorial Children’s Hospital in Cape Town, South Africa (SA). Face to face semi-structured interviews were conducted and themes were extracted using a thematic framework approach. Results: The knowledge of the aetiology of epilepsy was limited for most participants whose beliefs included medical, spiritual and traditional causes. Poor seizure control despite medication has resulted in an ongoing search for sources of cure and the right medication(s) and dose which impacts on adherence. The majority of participants showed limited understanding of what precision medicine is and did not fully understand the PME study. However, most felt that if properly implemented, these measures would be beneficial in caring for Children with Epilepsy (CWE). The mHealth devices introduced new feelings and challenges. The four themes which emerged were: 1) Cause of epilepsy: uncertainty and conflicting views; 2) Need for healing; 3) PME mHealth devices; 4) Feasibility of Feasibility of implementation of PME initiatives. Conclusions: The cause of epilepsy was generally misunderstood but caregivers felt that PM could help unlock the unknown cause of the refractory epileptic seizures. Most caregivers harbour insecurities about treatment efficacy and are in a constant search for optimal therapy. Adherence to medication is central to controlling seizures but was inconsistent for most participants for a number of reasons including health care access and uncertainty about the benefit gained. The mHealth devices, particularly the phone app, was perceived to be helpful especially in improving adherence but created an additional burden for many participants. This sub-study generated beneficial information for understanding caregivers’ current level of understanding of epilepsy and the PME initiatives and the potential benefits and challenges in future implementation of PM in SA.

Includes bibliographical references / There are a range of conditions, collectively known as fetal alcohol spectrum disorders (FASD), which result from the exposure of a developing fetus to alcohol. South Africa has among the highest rates of FASD reported in the world, especially among the impoverished communities in the Western Cape region, with rates of up to 208.8 per 1000 first grade learners being reported. The need for screening, surveillance and immediate prevention work has been stressed. Limited research has been conducted on understanding the experiences of parents who raise children with FASD. This is invaluable in understanding what needs, support, services, education and funding is required. The Foundation for Alcohol Related Research (FARR) recently conducted a FASD epidemiological study to assess the burden of FASD and guide the implementation of prevention work in high risk areas. Grade one learners from 14 West Coast schools were diagnosed, and their mothers received a diagnostic feedback and counselling session. The aim of the rese arch project was to explore the experiences of women who have received an FASD diagnosis for their child and to understand their comprehension, feelings and needs. Thirteen participants were recruited through FARR and semi-structured interviews were conducted at Vredenburg Private Hospital in the West Coast region of South Africa. Additionally, three community workers were interviewed. The data was analysed using a thematic content analysis approach and five themes were identified. The research identified that the social context in which these women live has caused them to fall victim to their circumstances, contributing to their drinking habits. Their experiences of living with an FASD child are difficult and most women feel guilty while others are in denial. Although these women know that alcohol was the cause of their child's problems, there were a number of misconceptions such as the amount of alcohol to cause harm, which parent was responsible and that drugs are safer than alcohol use during pregnancy. Furthermore, the mothers found it helpful to know the diagnosis. This helped them understand their child's problems. They felt strongly that they will abstain from alcohol use during pregnancy and that they will encourage other women to do the same. There was a need for further education and context-sensitive intervention work. This research will impact strategies to support families, help to improve services and guide prevention work in this area.

Background: A weekly pregnancy counselling clinic is held in conjunction with foetal medicine experts at Groote Schuur Hospital for women with pregnancies complicated by foetal anomalies. In cases with poor prognoses, termination of pregnancy (TOP) may be offered. The women receive genetic counselling where the ultrasound findings, invasive testing and TOP options are discussed. Decision-making is the focus of these sessions. The experiences and decision-making processes of the women in this clinic are poorly understood, therefore this project aims to explore these women's experiences and what factors influence their decision-making regarding TOP. Methods: Qualitative research, drawing on principles of phenomenology was used as the study design. The sample for this study are women who had a prenatal diagnosis of a serious congenital abnormality and were offered TOP. The women were identified using the Division of Human Genetics pregnancy counselling database at the University of Cape Town in South Africa. Semistructured face-to-face interviews with open-ended questions were used to collect the data and close-ended questions were used to obtain the demographic data. The interviews were recorded and transcribed verbatim. The data were analysed using a thematic data analysis approach. A total of 12 women were interviewed. Results: Five themes were identified in this study. These include "Health care services", "Home", "Being a woman", "Finding meaning", and "The aftermath". The healthcare services impacted the manner in which the women made sense of the ultrasound findings. Support (or lack of) from family and the community impacted on their decision-making. Stigma attached to having a child with a disability and/or stigma against TOP and partner relationships played a role. The women questioned their role as a woman and obligations of child-bearing. Finding meaning for the event was important and this process continued until after the delivery or after the child was born. Following the event having a burial and giving away the child's clothes were found to play a significant role in their adjustment. Discussion and Conclusion: The decision-making process was multifaceted and unique to each woman. They consulted their families, partners and community but in the end they made the final decision. The women considered a multitude of factors but it seems that there may be one deciding factor. This in depth exploration of the women's experiences has provided valuable insight into the decision-making process, which can be used to improve the services offered to patients.

Includes abstract. / Includes bibliographical references (leaves 127-134). / Alpha thalassaemia X-linked mental retardation (ATR-X) syndrome is a rare, X-linked intellectual disability syndrome with an estimated prevalence in the range of 1-9/1 000 000. The prevalence in South Africa (SA) is unknown; however in Cape Town there is one extended family with seven males who were clinically, and later molecularly, diagnosed with this condition. Due to the identification of the mutation in this family, carrier and prenatal testing is available. However, since the announcement in 2007 that testing is available, no individuals have presented themselves for their carrier status to be determined. The aim of this study was to investigate the reasons why females in this family have not presented for carrier testing.