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At a glance

It is a chromosomal disorder characterized by supernumerary X chromosomes in male subjects associated with infertility and hypogonadism. The clinical features include weaker muscles with poor muscle coordination, tall height, less body hair, genital hypodevelopment, breast growth, and reduced libido.

Synonyms

47-XXY Syndrome; Hypogonadotropic Hypogonadism; Klinefelter-Reifenstein Syndrome; Klinefelter-Reifenstein-Albright Syndrome; Seminiferous Tubule Dysgenesis; Xq Kline­felter Syndrome.

History

First described in 1942 by the American physicians H.F. Klinefelter, Jr., E. C. Reifenstein, Jr., and F. Albright. In 1956, identification of the extra X chromosome was first noticed. For your information, mice can also have the XXY Syndrome.

Incidence

Klinefelter Syndrome is one of the most common chromosomal disorders, occurring in 1:500 to 1:1,000 live births. It is a chromosomal disorder affecting only males. There is no racial predilection. This disorder is the most common chromosomal cause of male hypogonadism and infertility.

Genetic inheritance

Nondisjunction of sex chromosomes during maternal meiosis (53%) or paternal meiosis (47%) results in 47,XXY genotype classically, although variants such as XXYY, XXXY, and XXXXY, and mosaic patterns, such as XXX/XY, also exist.

Pathophysiology

Additional X chromosome(s) result in cognitive abnormalities and affect the development of secondary sexual characteristics (proportionally to the extra number of X chromosomes). Extra sex chromosomes usually result from an error of nondisjunction during parental gametogenesis. The primary testicular failure causes elevation of gonadotropin levels because of a lack of feedback inhibition on the pituitary gland. In addition to androgen deficiency, which causes eunuchoid body proportions with gynecomastia, there is an increased incidence of autoimmune disorders (eg, systemic lupus erythematosus, rheumatoid arthritis).

Diagnosis

It is recognized that 10% of Klinefelter cases are diagnosed prenatally. The first clinical features may appear in early childhood but more frequently during puberty with the absence of secondary sexual characters and the evidence of aspermatogenesis. The standard diagnostic method is the analysis of the chromosomal karyotype on lymphocytes. Previously, an analysis of the Barr body was common practice. To confirm mosaicism, it is also possible to analyze the karyotype using dermal fibroblasts or testicular tissue.

Clinical aspects

The clinical presentation is phenotypically male. Physical manifestations of this syndrome develop at puberty. The association between small testis after puberty and underdeveloped secondary sex characteristics (sparse facial and body hair in a tall male) helps guide the diagnosis. Affected men are infertile as a consequence of azoospermia caused by sclerosed seminiferous tubules. Patients may be tall with long limbs. Osteoporosis may lead to vertebral collapse and even scoliosis. Unless treated with exogenous testosterone starting at puberty, patients can become obese and develop diabetes mellitus. A recent study from Britain showed that these patients have a reduced life expectancy. The main reasons were peripheral ...

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