Klinefelter's syndrome

Abstract

Klinefelter’s syndrome (KS) is the most common sex chromosome disorder in men, affecting roughly 1 in 400–600 men throughout all ethnic groups (1,2) It is also the most common cause of primary testicular failure, resulting in impairments in both spermatogenesis and testosterone production. The hypogonadism associated with KS can range from mild to severe, leading to a marked variation in clinical presentation. Men with KS possess at least one additional or “supernumerary” X chromosome, resulting in a 47, XXY genotype. The clinical phenotype in the adult is that of severely impaired spermatogenesis (usually azoospermia) and varying degrees of hypogonadism, manifested by a tall body habitus with sparse body and facial hair, gynecomastia, diminished libido, and small testes. In childhood, common presenting features can include delayed speech development, learning difficulties at school, unusually rapid growth in mid-childhood, and truncal obesity. Laboratory analysis reveals low or low-normal serum testosterone and elevated serum gonadotropin levels, with follicle-stimulating hormone (FSH) elevated to a greater degree than luteinizing hormone (LH). The clinical diagnosis is confirmed using chromosomal analysis (karyotyping) of either peripheral blood leukocytes or tissue, which usually reveals a 47, XXY genotype, although, infrequently, additional X chromosomes may be present or an individual may be mosaic (47, XXY/46, XY). Treatment consists of testosterone therapy for improved virilization, sexual function, bone density, and quality of life. Gynecomastia is treated with cosmetic surgery after androgen replacement has begun. New approaches to the treatment of infertility, including intracytoplasmic injection of sperm aspirated from the testes, have been recently reported for KS patients and may be successful in the subset of patients in whom sperm are present on testicular biopsy. However, for most men with KS, artificial insemination with donor sperm or adoption remain the only options for fertility. This chapter summarizes the initial historical description of KS, as well as the current understanding of the pathophysiology, clinical manifestations, associated conditions, and treatment of individuals with KS. In addition, the effect of newly described assisted reproductive techniques on the potential for fertility in men with KS is discussed.