|Other names||XXY syndrome, Klinefelter's syndrome, Klinefelter-Reifenstein-Albright syndrome|
|Symptoms||Varied; include above average height, weaker muscles, poor coordination, less body hair, breast growth, small testicle size, less interest in sex, infertility.|
|Complications||Infertility, intellectual disability, autoimmune disorders, breast cancer, venous thromboembolic disease, osteoporosis|
|Usual onset||At fertilisation|
|Causes||Two or more X chromosomes in males|
|Risk factors||Older age of mother|
|Diagnostic method||Genetic testing (karyotype)|
|Treatment||Physical therapy, speech and language therapy, counseling|
|Prognosis||Nearly normal life expectancy|
|Frequency||1 in 500–1000 males|
|Named after||Harry Klinefelter|
Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Often, these symptoms are noticed only at puberty; although this is one of the most common chromosomal disorders, occurring in one to two per 1,000 live male births. It is named after American endocrinologist Harry Klinefelter, who identified the condition in the 1940s.   
The syndrome is defined by the presence of at least one extra X chromosome in addition to a Y chromosome yielding a total of 47 or more chromosomes rather than the usual 46. Klinefelter syndrome occurs randomly. The extra X chromosome comes from the father and mother nearly equally. An older mother may have a slightly increased risk of a child with KS. The syndrome is diagnosed by the genetic test known as a karyotype.   
Signs and symptoms
The Klinefelter syndrome has different manifestations and these will vary from one patient to another. Among the primary features are infertility and small, poorly functioning testicles. Often, symptoms may be subtle and many people do not realize they are affected. Whereas some other times symptoms are more prominent and may include weaker muscles, greater height, poor motor coordination, less body hair, gynecomastia (breast growth), and low libido. In the majority of the cases, these symptoms are noticed only at puberty.   
An estimated 60% of pregnancies with fetuses having Klinefelter syndrome spontaneously abort. Generally, the severity of the malformations is proportional to the number of extra X chromosomes present in the karyotype. For example, patients with 49 chromosomes (XXXXY) have a lower IQ and more severe physical manifestations than those with 48 chromosomes (XXXY). 
As babies and children, XXY males may have weaker muscles and reduced strength. They may sit up, crawl, and walk later than other infants. In average KS children will start walking at 18 months of age. They also have less muscle control and coordination than other boys of their age. 
During puberty, they show less muscular body, less facial and body hair, and broader hips. This is a direct consequence of the low levels of testosterone produced by KS subjects. Delays in motor development may occur, which can be addressed through occupational and physical therapies. As teens, XXY males may develop breast tissue, have weaker bones, and a lower energy level than other males. The testicles of affected males are usually less than 2cm in length (and always shorter than 3.5cm), 1cm in width, and 4ml in volume. XXY men may also have microorchidism (i.e., small testicles).  
By adulthood, they tend to become taller than average; with proportionally longer arms and legs, less-muscular bodies, more belly fat, wider hips, narrower shoulders. Some KS males will show little to no sign of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). Gynecomastia is present in approximately a third of affected individuals, a slightly higher percentage than in the XY population. Approximately 10% of XXY males have gynecomastia noticeable enough that they may choose to have surgery. Affected males are often infertile, or have reduced fertility. Advanced reproductive assistance is sometimes possible in order to produce an offspring since approximately 50% of males with Klinefelter syndrome can produce sperm.  
Some degree of language learning or reading impairment may be present, and neuropsychological testing often reveals deficits in executive functions, although these deficits can often be overcome through early intervention. It is estimated that 10% of those with Klinefelter syndrome are autistic. Additional abnormalities may include impaired attention, reduced organizational and planning abilities, deficiencies in judgment (often presented as a tendency to interpret non-threatening stimuli as threatening), and dysfunctional decision processing.  
The overall IQ tends to be lower than average. Language milestones may also be delayed, particularly when compared to other people their age. Between 25% to 85% of XXY males have some kind of language problem, such as delay in learning to speak, trouble using language to express thoughts and needs, problems reading, and trouble processing what they hear. They may also have a harder time doing work that involves reading and writing, but most hold jobs and have successful careers.  
Behavior and personality traits
Compared to individuals with a normal number of chromosomes, males affected by Klinefelter syndrome may display behavioral abnormalities. These are phenotypically displayed as higher level of anxiety and depression, mood dysregulation, impaired social skills, emotional immaturity during childhood or difficulty with frustration.    These neurocognitive abnormalities are most likely due to the presence of the extra X chromosome, as indicated by studies carried out on animal models carrying an extra X chromosome.
In 1995 a scientific study evaluated the psychosocial adaptation of 39 adolescents with sex chromosome abnormalities. It demonstrated that XXY males tend to be quiet, shy and undemanding; they are less self-confident, less active, and more helpful and obedient than other boys their age. They may struggle in school and sports, meaning they may have more trouble fitting in with other kids.  
As adults, KS males live lives similar to men without the condition; they have friends, families, and normal social relationships. Nonetheless, some individuals may experience social and emotional problems due to problems in childhood. They show a lower sex drive and low self esteem, in most cases due to the feminine characteristics that their bodies display.  
XXY males are more likely than other men to have certain health problems, such as autoimmune disorders, breast cancer, venous thromboembolic disease, and osteoporosis. In contrast to these potentially increased risks, rare X-linked recessive conditions are thought to occur less frequently in XXY males than in XY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically only carriers rather than affected by these X-linked recessive conditions.
Klinefelter syndrome is not an inherited condition. Maternal age is the only known risk factor. Women at 40 years have a four-times-higher risk of a child with Klinefelter syndrome than women aged 24 years.
The extra chromosome is retained because of a nondisjunction event during paternal meiosis I, maternal meiosis I, or maternal meiosis II (gametogenesis). The relevant nondisjunction in meiosis I occurs when homologous chromosomes, in this case the X and Y or two X sex chromosomes, fail to separate, producing a sperm with an X and a Y chromosome or an egg with two X chromosomes. Fertilizing a normal (X) egg with this sperm produces an XXY offspring (Klinefelter). Fertilizing a double X egg with a normal sperm also produces an XXY offspring (Klinefelter).
Another mechanism for retaining the extra chromosome is through a nondisjunction event during meiosis II in the egg. Nondisjunction occurs when sister chromatids on the sex chromosome, in this case an X and an X, fail to separate. An XX egg is produced, which when fertilized with a Y sperm, yields an XXY offspring. This XXY chromosome arrangement is one of the most common genetic variations from the XY karyotype, occurring in approximately one in 500 live male births. See also Triple X syndrome.
In mammals with more than one X chromosome, the genes on all but one X chromosome are not expressed; this is known as X inactivation. This happens in XXY males, as well as normal XX females. However, in XXY males, a few genes located in the pseudoautosomal regions of their X chromosomes have corresponding genes on their Y chromosome and are capable of being expressed.
The condition 48,XXYY or 48,XXXY occurs in one in 18,000–50,000 male births. The incidence of 49,XXXXY is one in 85,000 to 100,000 male births. These variations are extremely rare. Additional chromosomal material can contribute to cardiac, neurological, orthopedic, and other anomalies.
Approximately 15–20% of males with KS may have a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Often, symptoms are milder in mosaic cases, with regular male secondary sex characteristics and testicular volume even falling within typical adult ranges. Another possible mosaicism is 47,XXY/46,XX with clinical features suggestive of KS and male phenotype, but this is very rare. Thus far, only approximately 10 cases of 47,XXY/46,XX have been described in literature.
Random Versus Skewed X-inactivation
Women typically have two X chromosomes, with half of their X chromosomes switching off early in embryonic development. The same happens with people with Klinefelter's, including in both cases a small proportion of individuals with a skewed ratio between the two Xs.
The term "hypogonadism" in XXY symptoms is often misinterpreted to mean "small testicles", when it instead means decreased testicular hormone/endocrine function. Because of (primary) hypogonadism, individuals often have a low serum testosterone level, but high serum follicle-stimulating hormone and luteinizing hormone levels, hypergonadotropic hypogonadism. Despite this misunderstanding of the term, however, .
The standard diagnostic method is the analysis of the chromosomes' karyotype on lymphocytes. A small blood sample is sufficient as test material. In the past, the observation of the Barr body was common practice, as well. To investigate the presence of a possible mosaicism, analysis of the karyotype using cells from the oral mucosa is performed. Physical characteristics of a Klinefelter syndrome can be tall stature, low body hair, and occasionally an enlargement of the breast. Usually, a small testicle volume of 1–5 ml per testicle (standard values: 12–30 ml) occurs. During puberty and adulthood, low testosterone levels with increased levels of the pituitary hormones FSH and LH in the blood can indicate the presence of Klinefelter syndrome. A spermiogram can also be part of the further investigation. Often, an azoospermia is present, or rarely an oligospermia. Furthermore, Klinefelter syndrome can be diagnosed as a coincidental prenatal finding in the context of invasive prenatal diagnosis (amniocentesis, chorionic villus sampling). Approximately 10% of KS cases are found by prenatal diagnosis.
The symptoms of KS are often variable, so a karyotype analysis should be ordered when small testes, infertility, gynecomastia, long arms/legs, developmental delay, speech/language deficits, learning disabilities/academic issues, and/or behavioral issues are present in an individual.
The lifespan of individuals with Klinefelter syndrome appears to be reduced by around 2.1 years compared to the general male population. These results are still questioned data, are not absolute, and need further testing.
As the genetic variation is irreversible, no causal therapy is available. From the onset of puberty, the existing testosterone deficiency can be compensated by appropriate hormone-replacement therapy. Testosterone preparations are available in the form of syringes, patches, or gel. If gynecomastia is present, the surgical removal of the breast may be considered for both the psychological reasons and to reduce the risk of breast cancer.
The use of behavioral therapy can mitigate any language disorders, difficulties at school, and socialization. An approach by occupational therapy is useful in children, especially those who have dyspraxia.
Methods of reproductive medicine, such as intracytoplasmic sperm injection (ICSI) with previously conducted testicular sperm extraction (TESE), have led to men with Klinefelter syndrome producing biological offspring. By 2010, over 100 successful pregnancies have been reported using IVF technology with surgically removed sperm material from males with KS.
The syndrome was named after American endocrinologist Harry Klinefelter, who in 1942 worked with Fuller Albright and E. C. Reifenstein at Massachusetts General Hospital in Boston, Massachusetts, and first described it in the same year. The account given by Klinefelter came to be known as Klinefelter syndrome as his name appeared first on the published paper, and seminiferous tubule dysgenesis was no longer used. Considering the names of all three researchers, it is sometimes also called Klinefelter–Reifenstein–Albright syndrome. In 1956, Klinefelter syndrome was found to result from an extra chromosome. Plunkett and Barr found the sex chromatin body in cell nuclei of the body. This was further clarified as XXY in 1959 by Patricia Jacobs and John Anderson Strong. The first published report of a man with a 47,XXY karyotype was by Patricia Jacobs and John Strong at Western General Hospital in Edinburgh, Scotland, in 1959. This karyotype was found in a 24-year-old man who had signs of KS. Jacobs described her discovery of this first reported human or mammalian chromosome aneuploidy in her 1981 William Allan Memorial Award address.
Klinefelter syndrome has been identified in ancient burials. In August 2022, a team of scientists published a study of a skeleton found in Bragança, north-eastern Portugal, of a man who died around 1000 AD and was discovered by their investigations to have a 47,XXY karyotype. In 2021, investigation of the individual buried with the Suontaka sword, previously assumed to be a woman, concluded he was a male with Klinefelter syndrome.
This syndrome, evenly distributed in all ethnic groups, has a prevalence of approximately four subjects per every 10,000 (0.04%) males in the general population. However, it is estimated that only 25% of the individuals with Klinefelter syndrome are diagnosed throughout their lives. The rate of Klinefelter syndrome among infertile males is 3.1%. The syndrome is also the main cause of male hypogonadism.
- "What are common symptoms of Klinefelter syndrome (KS)?". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 25 October 2013. Archived from the original on 2 April 2015. Retrieved 15 March 2015.
- Simonetti, Luciane; Ferreira, Lucas G.A.; Vidi, Angela Cristina; Souza, Janaina Sena de; Kunii, Ilda S.; Melaragno, Maria Isabel; Mello, Claudia Berlim de; Carvalheira, Gianna; Dias Da Silva, Magnus R. (2021). "Intelligence Quotient Variability in Klinefelter Syndrome is Associated with GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern". Frontiers in Genetics. 12: 724625. doi:10.3389/fgene.2021.724625. PMC 8488338. PMID 34616429.
- "Klinefelter syndrome". rarediseases.info.nih.gov. Archived from the original on 15 April 2019. Retrieved 15 April 2019.
- "Klinefelter Syndrome (KS): Overview". nichd.nih.gov. Eunice Kennedy Shriver National Institute of Child Health and Human Development. 2013-11-15. Archived from the original on 18 March 2015. Retrieved 15 March 2015.
- "How many people are affected by or at risk for Klinefelter syndrome (KS)?". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 30 November 2012. Archived from the original on 17 March 2015. Retrieved 15 March 2015.
- "How do health care providers diagnose Klinefelter syndrome (KS)?". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 2012-11-30. Archived from the original on 17 March 2015. Retrieved 15 March 2015.
- "What are the treatments for symptoms in Klinefelter syndrome (KS)?". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 2013-10-25. Archived from the original on 15 March 2015. Retrieved 15 March 2015.
- "Is there a cure for Klinefelter syndrome (KS)?". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 30 November 2012. Archived from the original on 17 March 2015. Retrieved 16 March 2015.
- "Klinefelter syndrome". Genetics Home Reference. National Library of Medicine. 30 October 2012. Archived from the original on 15 November 2012. Retrieved 2 November 2012.
- Visootsak, Jeannie; Graham, John M Jr (October 2006). "Klinefelter syndrome and other sex chromosomal aneuploidies". Orphanet Journal of Rare Diseases. 1: 42. doi:10.1186/1750-1172-1-42. PMC 1634840. PMID 17062147.
- Klinefelter, H. F. (September 1986). "Klinefelter's syndrome: historical background and development". Southern Medical Journal. 79 (9): 1089–1093. doi:10.1097/00007611-198609000-00012. ISSN 0038-4348. PMID 3529433. Retrieved November 29, 2023.
- "Klinefelter Syndrome". Mayo Clinic. Archived from the original on 8 September 2020. Retrieved 27 August 2020.
- Kanakis, George A.; Nieschlag, Eberhard (September 2018). "Klinefelter syndrome: more than hypogonadism". Metabolism. 86: 135–144. doi:10.1016/j.metabol.2017.09.017. PMID 29382506. S2CID 3702209.
- Defendi, Germaine L (January 31, 2022). Rohena, Luis O (ed.). "Klinefelter Syndrome". Medscape. Drugs & Diseases: Pediatrics: Genetics and Metabolic Disease.
- "Klinefelter Syndrome". Eunice Kennedy Shriver National Institute of Child Health and Human Development. 24 May 2007. Archived from the original on 27 November 2012. Retrieved November 28, 2023.
- Zierler-Browm, Seena L (August 25, 2006). "Klinefelter's Syndrome: XXY Males". U.S. Pharmacist. West Palm Beach, Florida. 8: 43–51.
- Klinefelter HF (September 1986). "Klinefelter's syndrome: historical background and development". Southern Medical Journal. 79 (9): 1089–1093. doi:10.1097/00007611-198609000-00012. PMID 3529433.
- Denschlag D, Tempfer C, Kunze M, Wolff G, Keck C (October 2004). "Assisted reproductive techniques in patients with Klinefelter syndrome: a critical review". Fertility and Sterility. 82 (4): 775–9. doi:10.1016/j.fertnstert.2003.09.085. PMID 15482743.
- Graham, Johm M; Bashir, Anthony S; Stark, Rachel E; Silbert, Annette; Walzer, Stanley (June 1, 1998). "Oral and Written Language Abilities of XXY Boys: Implications for Anticipatory Guidance". Pedriatics. 81 (6): 795–806. doi:10.1542/peds.81.6.795. S2CID 26098458 – via American Academy of Pediatrics.
- Boone KB, Swerdloff RS, Miller BL, Geschwind DH, Razani J, Lee A, et al. (May 2001). "Neuropsychological profiles of adults with Klinefelter syndrome". Journal of the International Neuropsychological Society. 7 (4): 446–456. doi:10.1017/S1355617701744013. PMID 11396547. S2CID 145642384.
- GenePool (October 17, 2005). "Klinefelter syndrome". Clinical Genetics Specialist Library. Archived from the original on September 27, 2007. Retrieved November 29, 2023.
- Skakkebæk, Anne; Moore, Philip J.; Pedersen, Anders Degn; Bojesen, Anders; Kristensen, Maria Krarup; Fedder, Jens; Hertz, Jens Michael; Østergaard, John R.; Wallentin, Mikkel; Gravholt, Claus Højbjerg (November 9, 2018). "Anxiety and depression in Klinefelter syndrome: The impact of personality and social engagement". PLOS ONE. 13 (11): e0206932. doi:10.1371/journal.pone.0206932. ISSN 1932-6203. PMC 6226182. PMID 30412595.
- Skakkebæk, Anne; Moore, Philip J.; Pedersen, Anders Degn; Bojesen, Anders; Kristensen, Maria Krarup; Fedder, Jens; Laurberg, Peter; Hertz, Jens Michael; Østergaard, John Rosendahl; Wallentin, Mikkel; Gravholt, Claus Højbjerg (February 9, 2017). "The role of genes, intelligence, personality, and social engagement in cognitive performance in Klinefelter syndrome". Brain and Behavior. 7 (3): e00645. doi:10.1002/brb3.645. ISSN 2162-3279. PMC 5346527. PMID 28293480.
- de Vries, Annelou L.C.; Roehle, Robert; Marshall, Louise; Frisén, Louise; van de Grift, Tim C.; Kreukels, Baudewijntje P.C.; Bouvattier, Claire; Köhler, Birgit; Thyen, Ute; Nordenström, Anna; Rapp, Marion; Cohen-Kettenis, Peggy T. (September 2019). "Mental Health of a Large Group of Adults With Disorders of Sex Development in Six European Countries". Psychosomatic Medicine. 81 (7): 629–640. doi:10.1097/PSY.0000000000000718. ISSN 0033-3174. PMC 6727927. PMID 31232913.
- Conn, P. Michael (2013). Animal models for the study of human disease (First ed.). San Diego: Elsevier Science & Technology Books. p. 780. doi:10.1016/C2011-0-05225-0. ISBN 9780124159129. Archived from the original on September 10, 2017. Retrieved February 9, 2017.
- Bender, B. G.; Harmon, R. J.; Linden, M. G.; Robinson, A. (August 1995). "Psychosocial adaptation of 39 adolescents with sex chromosome abnormalities". Pediatrics. 96 (2 Pt 1): 302–308. doi:10.1542/peds.96.2.302. ISSN 0031-4005. PMID 7630689. S2CID 36072015. Retrieved November 29, 2023.
- Hultborn R, Hanson C, Köpf I, Verbiené I, Warnhammar E, Weimarck A (November–December 1997). "Prevalence of Klinefelter's syndrome in male breast cancer patients". Anticancer Research. 17 (6D): 4293–7. PMID 9494523.
- Gravholt, C.H.; et al. (2018). "Kleinfelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology". Endocrine Reviews. 39 (4): 389–423. doi:10.1210/er.2017-00212. PMID 29438472.
- "Klinefelter Syndrome – Inheritance Pattern". NIH – Genetics Home Reference. NIH. Archived from the original on 30 January 2017. Retrieved 27 May 2021.
- Bojesen A, Juul S, Gravholt CH (February 2003). "Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study". The Journal of Clinical Endocrinology and Metabolism. 88 (2): 622–6. doi:10.1210/jc.2002-021491. PMID 12574191.
- Tüttelmann F, Gromoll J (June 2010). "Novel genetic aspects of Klinefelter's syndrome". Molecular Human Reproduction. 16 (6): 386–95. doi:10.1093/molehr/gaq019. PMID 20228051.
- "Klinefelter Syndrome – Inheritance Pattern". NIH – Genetics Home Reference. NIH. Archived from the original on 30 January 2017. Retrieved 27 January 2017.
- Chow JC, Yen Z, Ziesche SM, Brown CJ (2005). "Silencing of the mammalian X chromosome". Annual Review of Genomics and Human Genetics. 6: 69–92. doi:10.1146/annurev.genom.6.080604.162350. PMID 16124854.
- Blaschke RJ, Rappold G (June 2006). "The pseudoautosomal regions, SHOX and disease". Current Opinion in Genetics & Development. 16 (3): 233–9. doi:10.1016/j.gde.2006.04.004. PMID 16650979.
- Linden MG, Bender BG, Robinson A (October 1995). "Sex chromosome tetrasomy and pentasomy". Pediatrics. 96 (4 Pt 1): 672–82. doi:10.1542/peds.96.4.672. PMID 7567329.
- Samplaski, Mary K.; et al. (April 2014). "Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients". Fertility and Sterility. 101 (4): 950–955. doi:10.1016/j.fertnstert.2013.12.051. PMID 24502895. Archived from the original on 11 October 2020. Retrieved 13 June 2020.
- Velissariou V, Christopoulou S, Karadimas C, Pihos I, Kanaka-Gantenbein C, Kapranos N, et al. (2006). "Rare XXY/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report". European Journal of Medical Genetics. 49 (4): 331–7. doi:10.1016/j.ejmg.2005.09.001. PMID 16829354.
- Kinjo K, Yoshida T, Kobori Y, Okada H, Suzuki E, Ogata T, Miyado M, Fukami M. Random X chromosome inactivation in patients with Klinefelter syndrome. Mol Cell Pediatr. 2020 Jan 24;7(1):1. doi: 10.1186/s40348-020-0093-x. PMID 31974854; PMCID: PMC6979883. Retrieved 09 August 2021.
- Leask, Kathryn (October 2005). "Klinefelter syndrome". National Library for Health, Specialist Libraries, Clinical Genetics. National Library for Health. Archived from the original on 2007-09-27. Retrieved 2007-04-07.
- Kamischke A, Baumgardt A, Horst J, Nieschlag E (Jan–Feb 2003). "Clinical and diagnostic features of patients with suspected Klinefelter syndrome". Journal of Andrology. 24 (1): 41–8. doi:10.1002/j.1939-4640.2003.tb02638.x. PMID 12514081. S2CID 25133531.
- Nieschlag E (May 2013). "Klinefelter syndrome: the commonest form of hypogonadism, but often overlooked or untreated". Deutsches Ärzteblatt International. 110 (20): 347–53. doi:10.3238/arztebl.2013.0347. PMC 3674537. PMID 23825486.
- Abramsky L, Chapple J (April 1997). "47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling". Prenatal Diagnosis. 17 (4): 363–8. doi:10.1002/(SICI)1097-0223(199704)17:4<363::AID-PD79>3.0.CO;2-O. PMID 9160389. S2CID 25935518.
- Bojesen A, Juul S, Birkebaek N, Gravholt CH (August 2004). "Increased mortality in Klinefelter syndrome". The Journal of Clinical Endocrinology and Metabolism. 89 (8): 3830–4. doi:10.1210/jc.2004-0777. PMID 15292313.
- Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA (December 2005). "Mortality in patients with Klinefelter syndrome in Britain: a cohort study". The Journal of Clinical Endocrinology and Metabolism. 90 (12): 6516–22. doi:10.1210/jc.2005-1077. PMID 16204366.
- Groth KA, Skakkebæk A, Høst C, Gravholt CH, Bojesen A (January 2013). "Clinical review: Klinefelter syndrome—a clinical update". The Journal of Clinical Endocrinology and Metabolism. 98 (1): 20–30. doi:10.1210/jc.2012-2382. PMID 23118429.
- Gabriele R, Borghese M, Conte M, Egidi F (2002). "[Clinical-therapeutic features of gynecomastia]". Il Giornale di Chirurgia (in Italian). 23 (6–7): 250–2. PMID 12422780.
- "What are the treatments for symptoms in Klinefelter syndrome (KS)?". nichd.nih.gov/. December 2016. Archived from the original on 2020-07-09. Retrieved 2020-07-14.
- Harold Chen. "Klinefelter Syndrome – Treatment". medscape.com. Archived from the original on 2 July 2012. Retrieved 4 September 2012.
- Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, et al. (May 2017). "Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis". Human Reproduction Update. 23 (3): 265–275. doi:10.1093/humupd/dmx008. PMID 28379559.
- Fullerton G, Hamilton M, Maheshwari A (March 2010). "Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009?". Human Reproduction. 25 (3): 588–97. doi:10.1093/humrep/dep431. PMID 20085911.
- Klinefelter HF Jr; Reifenstein EC Jr; Albright F. (1942). "Syndrome characterized by gynecomastia, aspermatogenesis without a-Leydigism and increased excretion of follicle-stimulating hormone". The Journal of Clinical Endocrinology & Metabolism. 2 (11): 615–624. doi:10.1210/jcem-2-11-615.
- The Klinefelter-Reifenstein-Albright syndrome. Archived 2017-08-27 at the Wayback Machine on biomedsearch.com, retrieved 26 August 2017
- Odom, Samuel L. (2009). Handbook of developmental disabilities (Pbk. ed.). New York: Guilford. p. 113. ISBN 9781606232484. Archived from the original on 2017-09-10. Retrieved 2017-09-02.
- Jacobs PA, Strong JA (January 1959). "A case of human intersexuality having a possible XXY sex-determining mechanism". Nature. 183 (4657): 302–3. Bibcode:1959Natur.183..302J. doi:10.1038/183302a0. PMID 13632697. S2CID 38349997.
- Jacobs PA (September 1982). "The William Allan Memorial Award address: human population cytogenetics: the first twenty-five years". American Journal of Human Genetics. 34 (5): 689–98. PMC 1685430. PMID 6751075.
- A 1000-year-old case of Klinefelter's syndrome diagnosed by integrating morphology, osteology, and genetics, Xavier Roca-Rada et al., The Lancet, Volume 400, Issue 10353, 27 August 2022 – 2 September 2022, Pages 691-692
- Moilanen, Ulla; Kirkinen, Tuija; Saari, Nelli-Johanna; Rohrlach, Adam B.; Krause, Johannes; Onkamo, Päivi; Salmela, Elina (2021-07-15). "A Woman with a Sword? – Weapon Grave at Suontaka Vesitorninmäki, Finland". European Journal of Archaeology. Cambridge University Press. 25: 42–60. doi:10.1017/eaa.2021.30. ISSN 1461-9571.
- Jacobs PA (1979). "Recurrence risks for chromosome abnormalities". Birth Defects Original Article Series. 15 (5C): 71–80. PMID 526617.
- Maclean N, Harnden DG, Court Brown WM (August 1961). "Abnormalities of sex chromosome constitution in newborn babies". Lancet. 2 (7199): 406–8. doi:10.1016/S0140-6736(61)92486-2. PMID 13764957.
- Visootsak J, Aylstock M, Graham JM (December 2001). "Klinefelter syndrome and its variants: an update and review for the primary pediatrician". Clinical Pediatrics. 40 (12): 639–51. doi:10.1177/000992280104001201. PMID 11771918. S2CID 43040200.
- Matlach J, Grehn F, Klink T (Jan 2012). "Klinefelter syndrome associated with goniodysgenesis". Journal of Glaucoma. 22 (5): e7-8. doi:10.1097/IJG.0b013e31824477ef. PMID 22274665. S2CID 30565002.
- Virginia Isaacs Cover (2012). Living with Klinefelter Syndrome, Trisomy X and 47,XYY: A Guide for Families and Individuals Affected by Extra X and Y Chromosomes. Virginia Isaacs Cover. ISBN 978-0-615-57400-4.