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Klinefelter syndrome, XXY

MedGen UID:
44033
Concept ID:
C0022735
Disease or Syndrome
Synonyms: 47,XXY; Klinefelter syndrome; Klinefelter's syndrome; Klinefelter's syndrome, XXY; XXY syndrome; XXY trisomy
SNOMED CT: Klinefelter's syndrome, XXY (405769009); XXY syndrome (405769009); Klinefelter's syndrome karyotype 47 XXY (405769009); XXY Klinefelter's syndrome (405769009); Klinefelter syndrome, XXY (405769009); Klinefelter syndrome (22053006); Klinefelter's syndrome (22053006)
 
Monarch Initiative: MONDO:0006823

Definition

Klinefelter syndrome is a chromosomal condition in boys and men that can affect physical and intellectual development. Most commonly, affected individuals are taller than average are unable to father biological children (infertile); however the signs and symptoms of Klinefelter syndrome vary among boys and men with this condition. In some cases, the features of the condition are so mild that the condition is not diagnosed until puberty or adulthood, and researchers believe that up to 75 percent of affected men and boys are never diagnosed.Boys and men with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone (primary testicular insufficiency). Testosterone is the hormone that directs male sexual development before birth and during puberty. Without treatment, the shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), decreased muscle mass, decreased bone density, and a reduced amount of facial and body hair. As a result of the small testes and decreased hormone production, affected males are infertile but may benefit from assisted reproductive technologies. Some affected individuals also have differences in their genitalia, including undescended testes (cryptorchidism), the opening of the urethra on the underside of the penis (hypospadias), or an unusually small penis (micropenis).Other physical changes associated with Klinefelter syndrome are usually subtle. Older children and adults with the condition tend to be somewhat taller than their peers. Other differences can include abnormal fusion of certain bones in the forearm (radioulnar synostosis), curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus).Children with Klinefelter syndrome may have low muscle tone (hypotonia) and problems with coordination that may delay the development of motor skills, such as sitting, standing, and walking. Affected boys often have learning disabilities, resulting in mild delays in speech and language development and problems with reading. Boys and men with Klinefelter syndrome tend to have better receptive language skills (the ability to understand speech) than expressive language skills (vocabulary and the production of speech) and may have difficulty communicating and expressing themselves.Individuals with Klinefelter syndrome tend to have anxiety, depression, impaired social skills, behavioral problems such as emotional immaturity and impulsivity, attention-deficit/hyperactivity disorder (ADHD), and limited problem-solving skills (executive functioning). About 10 percent of boys and men with Klinefelter syndrome have autism spectrum disorder.Nearly half of all men with Klinefelter syndrome develop metabolic syndrome, which is a group of conditions that include type 2 diabetes, high blood pressure (hypertension), increased belly fat, high levels of fats (lipids) such as cholesterol and triglycerides in the blood. Compared with unaffected men, adults with Klinefelter syndrome also have an increased risk of developing involuntary trembling (tremors), breast cancer (if gynecomastia develops), thinning and weakening of the bones (osteoporosis), and autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. (Autoimmune disorders are a large group of conditions that occur when the immune system attacks the body's own tissues and organs.)
[from GHR]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVKlinefelter syndrome, XXY

Professional guidelines

PubMed

Gregg AR, Skotko BG, Benkendorf JL, Monaghan KG, Bajaj K, Best RG, Klugman S, Watson MS
Genet Med 2016 Oct;18(10):1056-65. Epub 2016 Jul 28 doi: 10.1038/gim.2016.97. PMID: 27467454
Dondorp W, de Wert G, Bombard Y, Bianchi DW, Bergmann C, Borry P, Chitty LS, Fellmann F, Forzano F, Hall A, Henneman L, Howard HC, Lucassen A, Ormond K, Peterlin B, Radojkovic D, Rogowski W, Soller M, Tibben A, Tranebjærg L, van El CG, Cornel MC; European Society of Human Genetics.; American Society of Human Genetics.
Eur J Hum Genet 2015 Nov;23(11):1438-50. Epub 2015 Mar 18 doi: 10.1038/ejhg.2015.57. PMID: 25782669Free PMC Article

Suggested Reading

PubMed

Frühmesser A, Kotzot D
Sex Dev 2011;5(3):109-23. Epub 2011 Apr 29 doi: 10.1159/000327324. PMID: 21540567

Recent clinical studies

Etiology

Samango-Sprouse C, Lasutschinkow P, Powell S, Sadeghin T, Gropman A
Am J Med Genet A 2019 Mar;179(3):423-428. Epub 2019 Jan 13 doi: 10.1002/ajmg.a.61038. PMID: 30637954
Williams LA, Pankratz N, Lane J, Krailo M, Roesler M, Richardson M, Frazier AL, Amatruda JF, Poynter JN
Cancer 2018 Oct 1;124(19):3900-3908. Epub 2018 Oct 6 doi: 10.1002/cncr.31667. PMID: 30291793Free PMC Article
Samango-Sprouse C, Stapleton E, Chea S, Lawson P, Sadeghin T, Cappello C, de Sonneville L, van Rijn S
Am J Med Genet A 2018 Apr;176(4):877-885. Epub 2018 Feb 9 doi: 10.1002/ajmg.a.38621. PMID: 29423966
van Rijn S, de Sonneville L, Swaab H
Genes Brain Behav 2018 Jul;17(6):e12465. Epub 2018 Mar 22 doi: 10.1111/gbb.12465. PMID: 29406610
Dotters-Katz SK, Humphrey WM, Senz KL, Lee VR, Shaffer BL, Caughey AB
Eur J Obstet Gynecol Reprod Biol 2016 Aug;203:173-6. Epub 2016 Jun 9 doi: 10.1016/j.ejogrb.2016.05.006. PMID: 27318449

Diagnosis

Samango-Sprouse C, Lasutschinkow P, Powell S, Sadeghin T, Gropman A
Am J Med Genet A 2019 Mar;179(3):423-428. Epub 2019 Jan 13 doi: 10.1002/ajmg.a.61038. PMID: 30637954
Williams LA, Pankratz N, Lane J, Krailo M, Roesler M, Richardson M, Frazier AL, Amatruda JF, Poynter JN
Cancer 2018 Oct 1;124(19):3900-3908. Epub 2018 Oct 6 doi: 10.1002/cncr.31667. PMID: 30291793Free PMC Article
Samango-Sprouse C, Stapleton E, Chea S, Lawson P, Sadeghin T, Cappello C, de Sonneville L, van Rijn S
Am J Med Genet A 2018 Apr;176(4):877-885. Epub 2018 Feb 9 doi: 10.1002/ajmg.a.38621. PMID: 29423966
Rodrigues MA, Morgade LF, Dias LFA, Moreira RV, Maia PD, Sales AFH, Ribeiro PD
Genet Mol Res 2017 Sep 27;16(3) doi: 10.4238/gmr16039780. PMID: 28973759
Dotters-Katz SK, Humphrey WM, Senz KL, Lee VR, Shaffer BL, Caughey AB
Eur J Obstet Gynecol Reprod Biol 2016 Aug;203:173-6. Epub 2016 Jun 9 doi: 10.1016/j.ejogrb.2016.05.006. PMID: 27318449

Therapy

Sakurai T, Iizuka K, Kato T, Takeda J
Intern Med 2019 Jan 15;58(2):259-262. Epub 2018 Aug 24 doi: 10.2169/internalmedicine.1051-18. PMID: 30146555Free PMC Article
Flannigan R, Patel P, Paduch DA
Sex Med Rev 2018 Oct;6(4):595-606. Epub 2018 Apr 19 doi: 10.1016/j.sxmr.2018.02.008. PMID: 29680294
Kanakis GA, Nieschlag E
Metabolism 2018 Sep;86:135-144. Epub 2018 Jan 31 doi: 10.1016/j.metabol.2017.09.017. PMID: 29382506
Ross JL, Kushner H, Kowal K, Bardsley M, Davis S, Reiss AL, Tartaglia N, Roeltgen D
J Pediatr 2017 Jun;185:193-199.e4. Epub 2017 Mar 10 doi: 10.1016/j.jpeds.2017.02.036. PMID: 28285751Free PMC Article
Dotters-Katz SK, Humphrey WM, Senz KL, Lee VR, Shaffer BL, Caughey AB
Eur J Obstet Gynecol Reprod Biol 2016 Aug;203:173-6. Epub 2016 Jun 9 doi: 10.1016/j.ejogrb.2016.05.006. PMID: 27318449

Prognosis

Samango-Sprouse C, Lasutschinkow P, Powell S, Sadeghin T, Gropman A
Am J Med Genet A 2019 Mar;179(3):423-428. Epub 2019 Jan 13 doi: 10.1002/ajmg.a.61038. PMID: 30637954
Sciarra F, Pelloni M, Faja F, Pallotti F, Martino G, Radicioni AF, Lenzi A, Lombardo F, Paoli D
J Endocrinol Invest 2019 Jul;42(7):833-842. Epub 2018 Nov 29 doi: 10.1007/s40618-018-0989-7. PMID: 30499012
Franik S, Smeets D, van de Zande G, Gomes I, D'Hauwers K, Braat DDM, Fleischer K, Ramos L
Andrologia 2018 Jun;50(5):e13004. Epub 2018 Mar 7 doi: 10.1111/and.13004. PMID: 29512178
Samango-Sprouse C, Stapleton E, Chea S, Lawson P, Sadeghin T, Cappello C, de Sonneville L, van Rijn S
Am J Med Genet A 2018 Apr;176(4):877-885. Epub 2018 Feb 9 doi: 10.1002/ajmg.a.38621. PMID: 29423966
Samango-Sprouse C, Keen C, Sadeghin T, Gropman A
Prenat Diagn 2017 May;37(5):497-501. Epub 2017 Apr 17 doi: 10.1002/pd.5044. PMID: 28346690

Clinical prediction guides

Melogno S, Pinto MA, Badolato F, Sist E, Esposito A, Orsolini M, Tarani L
Am J Med Genet A 2019 Feb;179(2):183-189. Epub 2019 Jan 8 doi: 10.1002/ajmg.a.12. PMID: 30618195
Williams LA, Pankratz N, Lane J, Krailo M, Roesler M, Richardson M, Frazier AL, Amatruda JF, Poynter JN
Cancer 2018 Oct 1;124(19):3900-3908. Epub 2018 Oct 6 doi: 10.1002/cncr.31667. PMID: 30291793Free PMC Article
Franik S, Smeets D, van de Zande G, Gomes I, D'Hauwers K, Braat DDM, Fleischer K, Ramos L
Andrologia 2018 Jun;50(5):e13004. Epub 2018 Mar 7 doi: 10.1111/and.13004. PMID: 29512178
Samango-Sprouse C, Stapleton E, Chea S, Lawson P, Sadeghin T, Cappello C, de Sonneville L, van Rijn S
Am J Med Genet A 2018 Apr;176(4):877-885. Epub 2018 Feb 9 doi: 10.1002/ajmg.a.38621. PMID: 29423966
Rodrigues MA, Morgade LF, Dias LFA, Moreira RV, Maia PD, Sales AFH, Ribeiro PD
Genet Mol Res 2017 Sep 27;16(3) doi: 10.4238/gmr16039780. PMID: 28973759

Recent systematic reviews

Accardo G, Amoresano Paglionico V, Di Fraia R, Cittadini A, Salzano A, Esposito D, De Bellis A, Pasquali D
Expert Rev Endocrinol Metab 2019 Mar;14(2):145-152. Epub 2019 Feb 22 doi: 10.1080/17446651.2019.1584036. PMID: 30793993
Flannigan R, Patel P, Paduch DA
Sex Med Rev 2018 Oct;6(4):595-606. Epub 2018 Apr 19 doi: 10.1016/j.sxmr.2018.02.008. PMID: 29680294
Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, Ferlin A, Foresta C, Jannini EA, Maggi M, Lenzi A, Pasquali D, Francavilla S; Klinefelter ItaliaN Group (KING).
Hum Reprod Update 2017 May 1;23(3):265-275. doi: 10.1093/humupd/dmx008. PMID: 28379559
Mehta A, Paduch DA
Fertil Steril 2012 Aug;98(2):274-83. Epub 2012 Jun 23 doi: 10.1016/j.fertnstert.2012.06.001. PMID: 22732737
Denschlag D, Tempfer C, Kunze M, Wolff G, Keck C
Fertil Steril 2004 Oct;82(4):775-9. doi: 10.1016/j.fertnstert.2003.09.085. PMID: 15482743

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