Risk of trisomy 21 in offspring of patients with Klinefelter's syndrome

Summary Intracytoplasmic sperm injection (ICSI) has given some patients with Klinefelter's syndrome (ie, men with an XXY sex-chromosome profile) the chance to become fathers, but the genetic makeup of the spermatozoa used for the injection is a concern. We studied the segregation of the sex chromosomes and chromosomes 1 and 21 by multicolour fluorescence in-situ hybridisation in a patient with non-mosaic Klinefelter's syndrome who was a candidate for ICSI. As other workers have found, we saw a higher rate of 24,XX and 24,XY spermatozoa in the patient than in controls. However, we also found a much higher frequency of disomy 21 in the spermatozoa of this patient than in controls (6·2 vs 0·4%). Any child conceived by ICSI using this man's sperm will thus have a proportionally higher risk of trisomy 21.