A. Symptoms and Signs
Boys with an extra X chromosome are normal in appearance before puberty; thereafter, they have disproportionately long legs and arms, sparse body hair, a female escutcheon, gynecomastia, and small testes. Infertility is due to azoospermia; the seminiferous tubules are hyalinized. The incidence is 1 in 660 newborn males, but the diagnosis is often not made until a man is evaluated for inability to conceive. Intellectual disability is somewhat more common than in the general population. Many men with Klinefelter syndrome have language-based learning problems. However, their intelligence usually tests within the broad range of normal. As adults, detailed psychometric testing may reveal a deficiency in executive skills. The risk of osteoporosis, breast cancer, and diabetes mellitus is much higher in men with Klinefelter syndrome than in 46,XY men.
B. Laboratory Findings
Low serum testosterone is common. The karyotype is typically 47,XXY, but other sex chromosome anomalies cause variations of Klinefelter syndrome.
Screening for cancer (especially of the breast), deep venous thrombosis, and glucose intolerance is indicated.
Treatment with testosterone after puberty is advisable but will not restore fertility. However, men with Klinefelter syndrome have had mature sperm aspirated from their testes and injected into oocytes, resulting in fertilization. After the blastocysts have been implanted into the uterus of a partner, conception has resulted. But, men with Klinefelter syndrome do have an increased risk for aneuploidy in sperm, and therefore, genomic analysis of a blastocyst should be considered before implantation.
et al. Klinefelter syndrome in childhood: variability in clinical and molecular findings. J Clin Res Pediatr Endocrinol. 2018;10:100.
et al. Sperm retrieval in adolescents and young adults with Klinefelter syndrome: a prospective, pilot study. J Pediatr. 2016;170:260.e2.
et al. Androgen treatment effects on motor function, cognition, and behavior in boys with Klinefelter syndrome. J Pediatr. 2017;185:193.
et al. Klinefelter syndrome, cardiovascular system, and thromboembolic disease: review of the literature and clinical perspectives. Eur J Endocrinol. 2016;175:R27.
et al. Quality of life in men with Klinefelter syndrome: the impact of genotype, health, socioeconomics, and sexual function. Genet Med. 2018;20:214.