A cross-sectional online survey of quality of life in adults with Klinefelter syndrome in the UK

Abstract Klinefelter syndrome (KS) is the most common sex chromosome disorder in males and the leading genetic cause of hypogonadism, affecting approximately 1 in 450–600 male births. Despite its prevalence, many individuals remain undiagnosed. Although European cohort studies have demonstrated poorer health-related quality of life (HR-QoL) among individuals with KS, evidence from the United Kingdom remains limited. This cross-sectional online survey explored HR-QoL and perceived self-efficacy in clinical communication among adults with KS in the United Kingdom. Sixty adults with a confirmed diagnosis of KS were recruited through the Klinefelter Syndrome Association (UK). Participants completed validated measures of HR-QoL (WHOQOL-BREF) and Perceived Efficacy in Patient–Physician Interactions (PEPPI-5), alongside clinical and sociodemographic questions. Participants reported a broad range of physical and psychological comorbidities, with 32 (53%) of participants self-reporting depression and/or anxiety. Compared with UK normative data (N = 141), participants with KS demonstrated significantly lower HR-QoL scores across all WHOQOL-BREF domains. Linear regression analyses showed that greater perceived self-efficacy in clinician–patient communication was associated with better HR-QoL outcomes across all WHOQOL-BREF domains after adjustment for body mass index, comorbidity count, and self-reported depression and/or anxiety, with adjusted coefficients ranging from B = 4.06 to 6.98 WHOQOL points per 5-point increase in PEPPI-5 (P ≤ .022 for all domains). These findings highlight the substantial impact of KS on quality of life and emphasise the importance of interventions aimed at improving communication, supportive care, and patient engagement to enhance HR-QoL outcomes in adults with KS.