Context: Klinefelter syndrome is characterized by hypogonadism and infertility, consequent on the presence of extra X chromosome(s). There is limited information about long-term mortality in this syndrome because there have been no large cohort studies.
Objective: Our objective was to investigate mortality in men with Klinefelter syndrome.
Design and setting: We obtained data about patients diagnosed with Klinefelter syndrome at almost all cytogenetics centers in Britain, as far back as records were available, and conducted a cohort study of their mortality, overall and by karyotype.
Patients: We assessed 3518 patients diagnosed since 1959, followed to mid-2003.
Outcome measure: The outcome measure was standardized mortality ratio (SMR).
Results: A total of 461 deaths occurred. There was significantly raised mortality overall [SMR, 1.5; 95% confidence interval (CI), 1.4-1.7] and from most major causes of death including cardiovascular disease (SMR, 1.3; 95% CI, 1.1-1.5), nervous system disease (SMR, 2.8; 95% CI, 1.6-4.6), and respiratory disease (SMR, 2.3; 95% CI, 1.8-2.9). Mortality was particularly raised from diabetes (SMR, 5.8; 95% CI, 3.4-9.3), epilepsy (SMR, 7.2; 95% CI, 3.1-14.1), pulmonary embolism (SMR, 5.7; 95% CI, 2.5-11.3), peripheral vascular disease (SMR, 7.9; 95% CI, 2.9-17.2), vascular insufficiency of the intestine (SMR, 12.3; 95% CI, 4.0-28.8), renal disease (SMR, 5.0; 95% CI, 2.0-10.3), and femoral fracture (SMR, 39.4; 95% CI, 4.8-142.3). Mortality from ischemic heart disease was significantly decreased (SMR, 0.7; 95% CI, 0.5-0.9).
Conclusions: Patients diagnosed with Klinefelter syndrome have raised mortality from several specific causes. This may reflect hormonal and genetic mechanisms.