II. Epidemiology

  1. Most common major sexual differentiation abnormality
  2. Incidence of Klinefelter Syndrome in specific cohorts
    1. Newborn males: 1 in 500 to 1000
    2. Male Breast Cancer: 7.5%
    3. Infertile males: 3%
    4. Mild Mental Retardation: 1%

III. Pathophysiology

  1. Results in testicular dysgenesis
  2. Chromosomal abnormality with 47,XXY karyotype
    1. Abnormality of nondisjunction during meiosis
    2. Maternal or paternal origin
    3. Most of additional X Chromosome is inactivated
      1. Functioning extra genes confer Phenotype
      2. More severe cases with XXXY, XXXXY or XXYY
      3. Less severe cases with mosaicism (>1 cell line)

IV. Signs

  1. Late Eunuchoid body proportions
    1. Tall, slim and underweight
    2. Long legs and short torso
    3. Obesity and varicosities may occur in 33% of patients
  2. Hypergonadotropic Hypogonadism
    1. Testes small and firm (usually <2.0 cm or 2 ml)
    2. Penis small
    3. Azoospermia or Oligospermia (and Infertility)
  3. Other signs of Hypoandrogenism
    1. Gynecomastia (bilateral and painless)
    2. Decreased facial hair, but pubic hair abundant

V. Labs

  1. Karyotype: XXY
  2. Post-Puberty labs
    1. Follicle Stimulating Hormone (FSH) increased
    2. Leutinizing Hormone (LH) increased
    3. Inhibin B decreased
    4. Increased Estradiol to Testosterone ratio

VI. Associated Conditions

  1. Mild Mental Retardation
    1. Motor function delay
    2. Language comprehension problems
    3. Speech may also be affected
  2. Learning Disorders
    1. Attention Deficit Disorder
    2. Dyslexia
  3. Social maladjustment
  4. Mental illness
  5. Thyroid dysfunction
  6. Diabetes Mellitus
  7. Lung disease
  8. Breast Cancer (20x risk of healthy men)
  9. Osteoporosis

VII. Management: General

  1. Complete neurodevelopment evaluation at diagnosis
    1. Indicated if diagnosis in childhood
  2. Breast Cancer surveillance

VIII. Management: Testosterone Replacement after age 11

  1. Start
    1. Long acting Testosterone 25-50 mg IM q3-4 weeks
    2. Increase Testosterone dose by 50 mg q6-9 months
    3. Goal: 200 to 250 mg q3-4 weeks
  2. Maintenance
    1. Convert to Testosterone patches when at 200-250 mg

IX. Resources

  1. American Association for Klinefelter Syndrome
    1. http://www.aaksis.org
  2. Klinefelter Syndrome Support Group
    1. http://klinefeltersyndrome.org

X. References

  1. Mendoki (1991) J Am Acad Child Adolesc Psychiatry 30 [PubMed]
  2. Schwartz (1991) Endocrinol Metab Clin North Am 20:153 [PubMed]
  3. Smyth (1998) Arch Intern Med 158(12):1309-14 [PubMed]
  4. Behrman (2000) Nelson Pediatrics, Saunders, p. 1746-9
  5. Wattendorf (2005) Am Fam Physician 72:2259-62
  6. Wilson (1991) Harrison's Medicine, McGraw-Hill, p. 1800

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Related Studies

Ontology: Klinefelter Syndrome (C0022735)

Definition (MSHCZE) Onemocnění, při němž má muž dva (někdy více) chromozomy X. Je provázeno projevy hypogonadismu a některými dalšími abnormalitami. Ve většině případů je karyotyp 47 XXY, v některých případech jde o mozaiky či jinou kombinaci (např. 3 X chromozomy). Jedinci mají fenotypově mužské znaky, ale mají atrofii varlat s hyalinizací semenotvorných kanálků, jsou neplodní, v buňkách je přítomen sex chromatin. Časté jsou rovněž gynekomastie, opožděná puberta, změny kostí, ochlupení aj. Penis není výrazně zmenšen. Mají mnohdy vyšší hubenou postavu, mohou mít eunuchoidní rysy. Koncentrace gonadotropinů jsou zvýšeny (hypergonadotropní hypogonadismus). (cit. Velký lékařský slovník online, 2012 http://lekarske.slovniky.cz/ )
Definition (MEDLINEPLUS)

Klinefelter's syndrome is a condition that occurs in men who have an extra X chromosome in most of their cells. The syndrome can affect different stages of physical, language and social development. The most common symptom is infertility. Because they often don't make as much of the male hormone testosterone as other boys, teenagers with Klinefelter's syndrome may have less facial and body hair and may be less muscular than other boys. They may have trouble using language to express themselves. They may be shy and have trouble fitting in.

It is important to start treatment as early as possible. With treatment, most boys grow up to have normal sex lives, successful careers and normal social relationships.Treatments include

  • Educational services
  • Physical, speech and occupational therapy
  • Medical treatments including testosterone replacement

NIH: National Institute of Child Health and Human Development

Definition (NCI) A sex chromosome disorder caused by the presence of an extra X chromosome in the male karyotype. Affected individuals are infertile and have a small penis and testes. They tend to have tall stature and long legs and may have difficulties with speech and language development. Gynecomastia may be present.
Definition (NCI_NCI-GLOSS) A genetic disorder in males caused by having one or more extra X chromosomes. Males with this disorder may have larger than normal breasts, a lack of facial and body hair, a rounded body type, and small testicles. They may learn to speak much later than other children and may have difficulty learning to read and write. Klinefelter syndrome increases the risk of developing extragonadal germ cell tumors and breast cancer.
Definition (CSP) genetic disease that produces sterile males with small testes lacking sperm due to XXY karyotype.
Definition (MSH) A form of male HYPOGONADISM, characterized by the presence of an extra X CHROMOSOME, small TESTES, seminiferous tubule dysgenesis, elevated levels of GONADOTROPINS, low serum TESTOSTERONE, underdeveloped secondary sex characteristics, and male infertility (INFERTILITY, MALE). Patients tend to have long legs and a slim, tall stature. GYNECOMASTIA is present in many of the patients. The classic form has the karyotype 47,XXY. Several karyotype variants include 48,XXYY; 48,XXXY; 49,XXXXY, and mosaic patterns ( 46,XY/47,XXY; 47,XXY/48,XXXY, etc.).
Concepts Disease or Syndrome (T047) , Congenital Abnormality (T019)
MSH D007713
ICD9 758.7
ICD10 Q98.0 , Q98.4
SnomedCT 405769009, 22053006, 205701007, 157021007, 205696000, 405770005, 205712007, 268357008
English Syndrome, Klinefelter's, KLINEFELTER'S SYNDROME, Klinefelter's karyotype 47,XXY, Klinefelter's syndrome NOS, Klinefelter's syndrome karyotype 47,XXY, Klinefelter's syndrome, unspecified, Klinefelter's Syndrome, XXY trisomy, seminiferous tubule dysgenesis, seminiferous tubule dysgenesis (diagnosis), Klinefelter's syndrome (XXY), Klinefelter's syndrome (XXY) (diagnosis), Klinefelter Syndrome, 47,XXY complex intersex, 47,XXY complex intersex (diagnosis), intersex complex 47,XXY, Klinefelter syndrome, XXY, XXY Syndrome (Klinefelter Syndrome), Klinefelter syndrome, unspecified, Klinefelter Syndrome [Disease/Finding], klinefelter's syndrome, XXY, chromosome xxy syndrome, xxy syndrome, hypogonadotropic hypogonadism, klinefelter's syndrome, primary hypogonadism, klinefelter 's syndrome, klinefelter disease, klinefelters syndrome, klinefelter's syndromes, Syndrome, XXY, XXY Syndromes, XXY Syndrome, Syndromes, XXY, Hypogonadism, primary, Klinefelter Syndromes, Syndrome, Klinefelter, Syndromes, Klinefelter, klinefelter syndrome karyotype 47, xxy (diagnosis), Klinefelter syndrome karyotype 47, XXY, XXY male, Klinefelter syndrome (disorder), Klinefelter's syndrome NOS (disorder), XXY Klinefelter's syndrome (disorder), Klinefelter's syndrome (disorder), Klinefelter's Syndrome, XXY, XXY syndrome, Klinefelter's syndrome, Klinefelter syndrome, Klinefelter's syndrome karyotype 47 XXY, XXY Klinefelter's syndrome, Klinefelter's syndrome, XXY (disorder), Klinefelter's syndrome, XXY, Klinefelter, chromosome; anomaly, sex, Klinefelter, XXY; syndrome, hypogonadism; hypogonadotropic, hypogonadotropic; hypogonadism, karyotype; 47,XXY, Klinefelter, syndrome; XXY, anomaly; chromosomes, chromosomal, sex, Klinefelter, Klinefelters Syndrome, Hypogonadotropic Hypogonadism, klinefelter syndrome
Portuguese SINDROME DE KLINEFELTER, Síndrome XXY, Síndrome de Klinefelter
Spanish SINDROME DE KLINEFELTER, Síndrome XXY, síndrome de Klinefelter, síndrome de Klinefelter (trastorno), síndrome de Klinefelter, SAI (trastorno), síndrome de Klinefelter, SAI, síndrome XXY, síndrome de Klinefelter, XXY (trastorno), síndrome de Klinefelter, XXY, Síndrome de Klinefelter
Dutch XXY syndroom, XXY; syndroom, anomalie; chromosomen, chromosomaal, geslacht, Klinefelter, chromosoom; anomalie, geslacht, Klinefelter, hypogonadisme; hypogonadotroop, hypogonadotroop; hypogonadisme, karyotype; 47,XXY, Klinefelter, syndroom; XXY, Syndroom van Klinefelter karyotype 47,XXY, Syndroom van Klinefelter, niet gespecificeerd, syndroom van Klinefelter, Klinefelter, syndroom van, Klinefeltersyndroom, Syndroom van Klinefelter
French Syndrome XXY, SYNDROME DE KLINEFELTER, Syndrome de Klinefelter
German XXY Syndrom, KLINEFELTER SYNDROM, Klinefelter-Syndrom, Karyotyp 47,XXY, Klinefelter-Syndrom, nicht naeher bezeichnet, Klinefelter Syndrom, Klinefelter-Syndrom
Italian Sindrome XXY, Sindrome di Klinefelter
Japanese XXY症候群, XXYショウコウグン, クラインフェルターショウコウグン, Klinefelter症候群, クラインフェルター症候群
Swedish Klinefelters syndrom
Czech Klinefelterův syndrom, XXY syndrom, XX mužský syndrom, syndrom XXY
Finnish Klinefelterin oireyhtymä
Korean 클라인펠터 증후군, 핵형 47, XXY, 상세불명의 클라인펠터 증후군
Polish Zespół Klinefeltera, Zespół XXY
Hungarian Klinefelter-syndroma, Xxy syndroma
Norwegian Klinefelters syndrom, 47 XXY-syndrom, XXY-syndrom, XX-mann