Mortality in patients with Klinefelter syndrome in Britain: a cohort study.

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.