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Key Points

  • Results from meiotic nondisjunction that occurs in the sperm (44% of cases) or egg (56% of cases).

  • About 10% of all cases are diagnosed prenatally and 26% of cases are diagnosed postnatally. The majority of cases are never diagnosed, which suggests that symptoms are mild.

  • Incidence of 47, XXY is 1 in 500 to 1 in 800 male births. Incidence of 48, XXXY is 1 in 20,000.

  • No sonographic findings are characteristic. Nuchal translucency measurement may be increased.

  • The most significant factors regarding the decision whether or not to terminate the affected pregnancy are the presence of sonographic abnormalities and the medical specialty of the person providing the genetic counseling.

  • Affected males are tall, but phenotypically normal, with an increased risk for developmental delays in speech, neuromotor, and learning disabilites.

  • Testosterone treatment is recommended, beginning at puberty.

  • 50% to 80% of affected males develop gynecomastia, but it is usually mild.

  • Fertility is now possible with assisted reproductive technology.

  • Motor impairment and speech and language problems are more common if the extra X chromosome is paternally derived.


Klinefelter syndrome (47, XXY karyotype) is the spectrum of phenotypic features resulting from a sex chromosome complement that includes two or more X chromosomes and one Y chromosome (Figure 135-1). It results from meiotic nondisjunction occurring during gametogenesis of the egg or sperm with subsequent fertilization of an XX ovum by a Y bearing sperm, or fertilization of an X ovum by a sperm bearing both the X and Y chromosomes (Mandoki et al., 1991). There are no known predisposing factors except advanced maternal age in some, but not all, cases. The condition was first described in nine men with gynecomastia, infertility with normal Leydig cells, a normal to low 17-ketosteroid level, and a high follicle stimulating hormone level in the urine (Klinefelter et al., 1942); Schwartz and Root, 1991). It was not until 1956 that the chromosomal basis of this abnormality was appreciated by noting the presence of the Barr body on buccal smears obtained from affected patients, which represented the inactive extra X chromosome (Arens et al., 1988). The specific chromosomal abnormality reponsible for the disorder was not known until 1959.

Figure 135-1

Karyotype obtained from a patient with Klinefelter syndrome, demonstrating presence of two X and one Y chromosomes. (Courtesy of Dr. Janet Cowan.)

The phenotype in Klinefelter syndrome is extremely variable and may be subtle. Most cases are never diagnosed. In general, affected males are identified by age-related clinical concerns (Table 135-1). Infant patients are identified by either prenatal cytogenetic testing for advanced maternal age or by the presence of mild genital abnormalities (Schwartz and Root, 1991). During school-age years, affected patients may be identified by the occurrence of learning ...

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