Klinefelter’s syndrome

Abstract When in 1942 Harry Klinefelter and his colleagues described the condition carrying his name (1), its aetiology was unknown. In 1959 Jacobs and Strong (2) recognized the chromosomal basis of the disorder, until then solely defined through a set of clinical criteria. Ever since, diagnosing Klinefelter’s syndrome has required the demonstration of the 47,XXY karyotype or one of its rare variants. The occasional patient with a normal karyotype who fulfils the original clinical criteria, namely small testes, azoospermia, gynaecomastia, and elevated urinary FSH, is no longer considered as having Klinefelter’s syndrome (3). Individuals with the karyotypes 48,XXYY, 48,XXXY, and 49,XXXXY are also subsumed under the Klinefelter’s syndrome category. While these patients display all the signs and symptoms typical of the 47,XXY karyotype, they are burdened by significant additional health problems, most notably mental retardation, and malformations. For this reason, these conditions should be designated as 48,XXYY, 48,XXXY, or 49,XXXXY syndromes, respectively, and should be set apart from Klinefelter’s syndrome in the narrower sense.