There are frequent discussions in Facebook groups regarding the question on whether KS and XXY represent the same or different conditions. AXYS has had the opportunity to discuss this with several physicians and research scientists that are considered experts in the field and would like to share their information below:

Dr. Harry Klinefelter was a physician and endocrinologist at Massachusetts General Hospital who originally described a syndrome in 1942 that was based on 9 patient case histories and examinations. The primary common characteristics he found in this group included small testes, sterility, increased FSH levels and gynecomastia. He wrote a paper titled, “Syndrome Characterized by Gynecomastia, Aspermatogenesis without A-Leydigism, and Increased Excretion of Follicle-Stimulating Hormone”. The term Klinefelter Syndrome was later adopted to describe these clinical characteristics. Chromosome technology was not yet available so genetic profiles were not part of the original syndrome.

By the late 1950’s, chromosome technology had improved and it was determined that individuals with KS characteristics frequently had a genetic signature of 47,XXY. It was also recognized there were 47,XXY individuals that sometimes had other common characteristics outside of the typical clinical presentation of tall stature, small testes, sterility and increased FSH levels. This included blood disorders, osteoporosis, anxiety and depression, speech and learning disorders, etc. In addition, there was a wide range of body shapes and sizes.

The term KS was in common use in the medical literature by this time, so scientists simply expanded their definition of KS to include the new characteristics and phenotypes that were found to be associated with the genetic signature of 47,XXY. They did not limit the use of the KS term to just identify individuals that demonstrated the original classic endocrinology characteristics…..they applied the term to anyone that was determined to have a 47,XXY signature.

Dr Klinefelter published a second paper in 1986 that briefly discussed this issue of chromosome analysis and genetic signatures. He suggested all 47,XXY individuals should actually be identified as having Klinefelter’s disease which would help distinguish them from other people that have the endocrinology characteristics of KS but do not have a genetic signature of 47,XXY. He was very much aware by then that 47,XXY individuals had a wide range of phenotypes (physical and clinical characteristics) and felt it was appropriate to use the term KS or 47,XXY to describe these individuals, regardless of the exact clinical characteristics they expressed. The one constant in all of these individuals was their genetic signature of 47,XXY.
His suggestion was never adopted so the medical profession has continued to use the KS and XXY terms equally. Some non-medical people would prefer to use these terms differently, but this is not how it is recognized by the medical or research communities…..KS and 47,XXY remain synonymous.

Written by Gary Glissman (AXYS USA)