Only rarely are patients with the Klinefelter syndrome fertile, and presumably such persons are mosaics with a large proportion of 46,XY cells. The sterility is due to impaired spermatogenesis, sometimes to the extent of total azoospermia. Histologic examination shows hyalinization of tubules, which appear as ghostlike structures on tissue section. By contrast, Leydig cells are prominent, as a result of either hyperplasia or an apparent increase related to loss of tubules. Although Klinefelter syndrome may be associated with mental retardation, the degree of intellectual impairment typically is mild, and in some cases, no deficit is detectable. The reduction in intelligence is correlated with the number of extra X chromosomes. Klinefelter syndrome is associated with a higher frequency of several disorders, including breast cancer (seen 20 times more commonly than in normal males), extragonadal germ-cell tumors, and autoimmune diseases such as systemic lupus erythematosus.
Turner syndrome, characterized by primary hypogonadism in phenotypic females, results from partial or http://ebooksmedicine.net complete monosomy of the short arm of the X chromosome. With routine cytogenetic methods, the entire X chromosome is found to be missing in 57% of patients, resulting in a 45,X karyotype. These patients are the most severely affected, and the diagnosis often can be made at birth or early in childhood. Typical clinical features associated with 45,X Turner syndrome include growth retardation, leading to abnormally short stature (below the third percentile); swelling of the nape of the neck because of distended lymphatic channels (in infancy) that is seen as webbing of the neck in older children; low posterior hairline; cubitus valgus (an increase in the carrying angle of the arms); shieldlike chest with widely spaced nipples; high-arched palate; lymphedema of the hands and feet; and a variety of congenital malformations such as horseshoe kidney, bicuspid aortic valve, and coarctation of the aorta (
Fig. 7.16 ). Cardiovascular abnormalities are the most common cause of death in childhood. In adolescence, affected girls fail
Coarctation of aorta Broad chest
Streak ovaries, infertility, amenorrhea
Incidence: 1 in 3000 female births Karyotypes: Classic: 45,X Defective second X chromosome: 46,X,i(Xq) 46,XXq– 46,XXp– 46,X, r(X) Mosaic type: 45,X/46,XX
Fig. 7.16 ClinicalfeaturesandkaryotypesofTurnersyndrome.
to develop normal secondary sex characteristics; the genitalia remain infantile, breast development is minimal, and little pubic hair appears. Most patients have primary amenorrhea, and morphologic examination shows transformation of the ovaries into white streaks of fibrous stroma devoid of follicles. The mental status of these patients usually is normal, but subtle defects in visual–spatial information processing have been noted. Curiously, hypothyroidism caused by autoantibodies occurs, especially in women with isochromosome Xp. As many as 50% of these patients develop clinical hypothyroidism. In adult patients, a combination of short stature and primary amenorrhea should prompt strong suspicion for Turner syndrome. The diagnosis is established by karyotyping.