The burden of disease for children diagnosed with Klinefelter syndrome – a European cohort

Abstract Background Klinefelter syndrome is a congenital chromosomal anomaly, where males have an extra X-chromosome. The syndrome may be associated with hypergonadotropic hypogonadism and many are late or undiagnosed. This European, population-based data-linkage cohort study was part of the EUROlinkCAT project and investigated the burden of disease for the first ten years of life for European children diagnosed with Klinefelter syndrome. Results Thirteen national and regional population-based registries in ten countries from the European surveillance of congenital anomalies (EUROCAT) network participated. Data for live born children born in 1995-2014 and diagnosed with Klinefelter syndrome prenatally or during infancy were linked to mortality and hospital records. Data for liveborn children born with any congenital anomaly and children without a congenital anomaly (reference children) were included for comparison on morbidity. Out of 5.8 million live born children 278 were diagnosed with Klinefelter syndrome in the 13 registry areas, 96.8% survived the first 5 year of life, 64.7% (95% CI 51.8;75.0) were admitted to hospital during the first year with a median length of stay of 3.9 (95% CI 3.0;4.7) days, 10.8% (95% CI 6.9;16.4) had a hospital stay of ≥10 days and 12.3% (95% CI 7.1;18.9) underwent surgery. In the age group 1-4 years of age 53.5% (95% CI 41.2;64.4) were admitted to hospital, the median length of stay decreased to 0.7 (95% CI 0.3;1.1) days and 6.3% (95% CI 2.6;12.3) had a hospital stay of ≥ 10 days. Conclusions More children diagnosed prenatally or in infancy with Klinefelter syndrome were hospitalised and underwent more surgery compared to reference children, while less were hospitalised and fewer had surgery than all children with any other congenital anomaly. Thus, the burden of disease was increased for children diagnosed prenatally or in infancy with Klinefelter syndrome but decreased overall after the first year of life.