Different Karyotypes, Same Disease?
High grade aneuploidies of the sex chromosomes (HGA) presenting with a male phenotype comprise a vast and heterogenous group of very rare conditions, once considered as “variants” of Klinefelter syndrome (KS). This association with KS was mainly based on the presence of at least one supernumerary X chromosome, high stature and hypergonadotropic hypogonadism with severe testicular hypotrophy. However, many of the shared features show elevated severity in HGA compared to KS, while many others are unique to HGA. Different karyotypes arise from mechanisms peculiar to each HGA syndrome.