OBJECTIVES: To determine whether older paternal age increases the risk of 
fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter 
(XXY) or XYY syndrome.
DESIGN: Case-control: cases with each of these syndromes were matched to four 
controls with Down syndrome from within the same congenital anomaly register and 
with maternal age within 6 months.
SETTING: Data from 22 EUROCAT congenital anomaly registers in 12 European 
countries.
PARTICIPANTS: Diagnoses with observed or (for terminations) predicted year of 
birth from 1980 to 2005, comprising live births, fetal deaths with gestational 
age ≥ 20 weeks and terminations after prenatal diagnosis of the anomaly. Data 
include 374 cases of Patau syndrome, 929 of Edwards syndrome, 295 of Klinefelter 
syndrome, 28 of XYY syndrome and 5627 controls with Down syndrome.
MAIN OUTCOME MEASURES: Odds ratio (OR) associated with a 10-year increase in 
paternal age for each anomaly was estimated using conditional logistic 
regression. Results were adjusted to take account of the estimated association 
of paternal age with Down syndrome (1.11; 95% CI 1.01 to 1.23).
RESULTS: The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards 
syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); 
and for XYY syndrome, 1.99 (0.75 to 5.26).
CONCLUSIONS: There was a statistically significant increase in the odds of 
Klinefelter syndrome with increasing paternal age. The larger positive 
associations of Klinefelter and XYY syndromes with paternal age compared with 
Patau and Edwards syndromes are consistent with the greater percentage of these 
sex chromosome anomalies being of paternal origin.