Endocrine Abstracts

Introduction: KS prevalence is estimated to range from 0.1-0.2 % in men and actually the estimated frequency is of about 1:500 to 1:1000 men¹. However, the real prevalence remains unknown due also to the fact that the disease is often overlooked and undermanaged¹.

Aim and methods: We performed a systematic literature search including studies published between 1971 and January 2024 to investigate the real prenatal prevalence of KS (including both pure and mosaic karyotypes) among chromosome abnormalities (CAs) and sex CAs (SCAs) diagnosed by different IPDs procedures (i.e. chorionic villus sampling, amniocentesis, and cordocentesis). The primary endpoint was the prevalence of KS. No specific criteria for study populations were provided.

Results: Among the 1826 studies detected by the literature search, 59 matched our inclusion criteria, considering so far 776912 IPD procedures, most of them performed for medical indication (88%). A total of 24094 CAs (3.10%) diagnosis were reported, of which 3729, (15.48%), was due to SCAs (i.e. 45,X0; 47,XXY; 47,XXX; 47,XYY). KS was diagnosed in 1074 out of 776912 fetuses, and as expected was the most prevalent SCA in males (median 0.13%, range 0-9.28%), with 46,XY/47,XXY accounting for 8.41% of all KS. Despite a high heterogeneity between studies, KS was mainly reported when genetic tests were performed in the presence of any gynecological indication (median of 0.13% vs 0.01%) (P<0.0001). Moreover, KS cases among CAs were more common when IPD procedures were performed due to any medical indication than without (3.32% vs 0%). A significant association between KS and mother’s age at birth was confirmed, hence the median >35/<35 y/o ratio was 1.07 (range 0-3.07).

Conclusions: This study confirms that around 1.3 of 1000 men (0.65/500) may be affected by KS, which is in line with data suggested by the literature. As the vast majority of KS diagnosis have been done after a gynecological indication, it is possible that this prevalence overestimates the prevalence rate in general population. Further studies are needed to analyze the prevalence of KS in the overall population. To our knowledge this is the widest systematic synthesis and confirms the association reported between KS and CAs’ risk factors (e.g. advanced mother age, abnormal US).

Reference: 1. Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A; Klinefelter ItaliaN Group (KING). Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest. 2017, doi: 10.1007/s40618-016-0541-6.