Long-term Systematic Follow-up of Patients With Klinefelter Syndrome Followed at the Department of Growth and Reproduction, Rigshospitalet

Klinefelter syndrome (KS) is the most frequent sex chromosome disorder affecting approximately 1:660 newborn boys. The prevalence of KS rises to 3-4% among infertile males and 10-15% in patients with non-obstructive azoospermia. KS is highly underdiagnosed, and diagnosis is often delayed. Phenotypic variability, and especially a presentation with mild clinical features, often leads to diagnostic delay or non-diagnosis. It has been estimated that 50-75% of males with KS never obtain a diagnosis (Berglund et al., 2019; Bojesen et al., 2003). Despite increasing interest in studying KS during recent years there remain significant gaps in our overall understanding of KS, including when and how to start testosterone replacement therapy (TRT), how to prevent co-morbidities, mechanisms of complications, success of fertility preservation and assessment of quality of life in affected individuals. This translates into differences in standards of care for these patients, with substantial variability in clinical practice. International guidelines regarding the care of patients with KS were published by the European Academy of Andrology/European Society of Endocrinology in 2021 (Zitzmann et al., 2021) to improve the clinical care of these patients. These guidelines, however, are limited by a general lack of scientific evidence due to the low number of studies in the field. This increases the need to systematically collect more information to develop individualized and optimized care for future patients. The investigators therefore aim to systematically describe the phenotype of Klinefelter syndrome throughout life by collecting clinical, biochemical, genetic, and radiological data on reproductive development, fertility, anthropometry, bone age, body composition, bone mineralization, co-morbidities, biomarkers of general health as well as psychopathology and mental health. Hypotheses: 1. Patients with KS may differ from controls in their biological health profile (hormonal, th