klinefelter syndrome klinefelter syndrome 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. usually, symptoms are subtle and subjects do not realize they are affected. sometimes, symptoms are more evident and may include weaker muscles, greater height, poor motor coordination, less body hair, breast growth, and less interest in sex. often, these symptoms are noticed only at puberty. intelligence is usually average, but reading difficulties and problems with speech are more common. not to be confused with xyy syndrome. klinefelter syndromeother namesxxy syndrome, klinefelter's syndrome, klinefelter-reifenstein-albright syndrome47,xxy karyotypepronunciation/ˈklaɪnfɛltər/ specialtymedical geneticssymptomsabove average height, weaker muscles, poor coordination, less body hair, breast growth, less interest in sex, infertility.complicationsinfertility, autoimmune disorders, breast cancer, venous thromboembolic disease, osteoporosisusual onsetat fertilisationdurationlong termcausestwo or more x chromosomes in malesrisk factorsolder motherdiagnostic methodgenetic testing (karyotype)preventionnonetreatmentphysical therapy, speech and language therapy, counselingprognosisnearly normal life expectancyfrequency1:500 to 1:1,000 males 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 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. ks is diagnosed by the genetic test known as a karyotype. while no cure is known, a number of treatments may help. physical therapy, occupational therapy, speech and language therapy, counselling, and adjustments of teaching methods may be useful. testosterone replacement may be used in those who have significantly lower levels. enlarged breasts may be removed by surgery. approximately half of affected males have a chance of fathering children with the help of assisted reproductive technology, but this is expensive and not risk free. xxy males have a ~15-fold higher risk of developing breast cancer than typical, but still lower than that of females. people with the condition have a nearly normal life expectancy. klinefelter syndrome 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. in 1956, the extra x chromosome was identified as the cause. mice can also have the xxy syndrome, making them a useful research model. signs and symptoms a person with typical untreated klinefelter 46,xy/47,xxy mosaic, diagnosed at age 19 – the scar from biopsy may be visible on his right breast above the nipple. the primary features are infertility and small, poorly functioning testicles. often, symptoms may be subtle and many people do not realize they are affected. sometimes, symptoms are more prominent and may include weaker muscles, greater height, poor coordination, less body hair, breast growth, and low libido. often, these symptoms are noticed only at puberty. prenatal an estimated 60% of pregnancies with fetuses having klinefelter syndrome abort. physical as babies and children, xxy males may have weaker muscles and reduced strength. as they grow older, they tend to become taller than average. they may have less muscle control and coordination than other boys of their age. during puberty, the physical traits of the syndrome become more evident; because these boys do not produce as much testosterone as other boys, they have a less muscular body, less facial and body hair, and broader hips. as teens, xxy males may develop breast tissue and also have weaker bones, and a lower energy level than other males. by adulthood, xxy males look similar to males without the condition, although they are often taller. in adults, possible characteristics vary widely and include 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 cosmetic surgery. affected males are often infertile, or have reduced fertility. advanced reproductive assistance is sometimes possible. an estimated 50% of males with klinefelter syndrome can produce sperm. 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, xxy men may also have microorchidism (i.e., small testicles). the testicles of affected males are usually less than 2 cm in length (and always shorter than 3.5 cm), 1 cm in width, and 4 ml in volume. 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. cognitive and developmental 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. also, delays in motor development may occur, which can be addressed through occupational and physical therapies. xxy males may sit up, crawl, and walk later than other infants; they may also struggle in school, both academically and with sports. 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. compared to individuals with a normal number of chromosomes, males affected by klinefelter's syndrome may display behavioral abnormalities. these are phenotypically displayed as higher level of anxiety and depression, and mood dysregulation. 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. cause birth of a cell with karyotype xxy due to a nondisjunction event of one x chromosome from a y chromosome during meiosis i in the male birth of a cell with karyotype xxy due to a nondisjunction event of one x chromosome during meiosis ii in the female 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 for 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.