An exploration of the prevalence and psychosocial aspects of Klinefelter Syndrome in the context of population-based genetic screening.

Klinefelter Syndrome (KS) is a genetic condition (47,XXY) affecting males and resulting in a spectrum of clinical features, ranging from azoospermia, small testes, breast development, testosterone deficiency, and decreased body and facial hair to varying levels of cognitive, social, behavioural and learning difficulties. The phenotype can be highly variable between individuals, and genetic factors such as functionality of the androgen receptor have been postulated to play a role. The prevalence of KS has previously been estimated at 1 in 650 male births, yet up to 70% remain undiagnosed. Early identification has long been advocated so that suitable interventions may be implemented at the optimal time. However, the only way of ensuring this would occur is through population-based genetic screening. This thesis examines the risks and benefits of diagnosing an individual with KS through population-based genetic screening at different ages. While there has been a significant body of research exploring the medical aspects of the condition, almost no evidence exists regarding the personal impact of KS. Not only is there a need to explore these issues, there is also recent evidence from the UK that the prevalence of KS is increasing. The prevalence of KS in Victoria, Australia, was estimated to be 1 in 450 male births, with a diagnosis rate of 50% of all males with the condition. A mixed methodology was utilised to determine the psychosocial impact of KS, the influence on adult quality of life of age at diagnosis, treatment and other interventions, and the attitudes of men with KS towards optimal age for diagnosis, screening, and therapeutic interventions. The influence of genetic factors was also examined. A population-based sample of adult men with KS from across Australia was recruited through multiple sources. Eighty-seven participants completed a written questionnaire, 79 provided a saliva sample for genetic analysis and 77 agreed to take part in an interview. Compared to population normative data, there was strong evidence (p<0.001) for the KS cohort having poorer outcomes for subjective well-being, body image, self-esteem, and mental health. The main predictors of this decrease in psychosocial health were unemployment, less social support and increased phenotypic severity. Those diagnosed later in life reported similar levels of health and behavioural problems as those diagnosed earlier in life. As such, age at diagnosis was found to have little association with psychosocial outcomes, after adjusting for confounders. Seventy-two percent of participants were diagnosed as adults, and 66% of these wished they had been diagnosed earlier. Two thirds of all participants supported population screening for KS. Androgen receptor CAG repeat length was associated with relationship status, waist circumference and one aspect of body image, however no association was observed between this polymorphism and the psychosocial outcomes measured. For men with KS, there is a measurably negative psychosocial impact of having this condition. Current stereotypes about the phenotype based on age at diagnosis may not be accurate. Efforts towards increased information, support, education and awareness of KS may yield important health benefits. The possibility of earlier diagnosis through population screening should be considered, taking into account the risks and benefits of this using available frameworks.