of puberty do not progress normally. This leads to the classic phenotype of KS: long legs, with an arm span frequently greater than height, gynecomastia, decreased muscle mass and increased abdominal adiposity, decreased facial and body hair, and small testes—which often measure less than 5 mL in volume (see Fig. 2). The penis may be decreased in size but is often of normal length. Gynecomastia is variable but is often prominent and may require surgical correction. Mosaicism may present more subtly, because affected individuals can appear anywhere along a phenotypic spectrum between classical KS and "normal." Infertility is almost universal; however, human leukocyte antigen (HLA)-confirmed children fathered by individuals with KS have been reported (19). Moreover, assisted reproductive techniques may allow some men with KS to father children (see section on KS and infertility). The frequency of various symptoms and signs of KS is summarized in Table 2.
Hormonally, the majority of affected men have decreased total testosterone levels, and those with normal total testosterone levels may, in fact have decreased free testosterone, because serum sex hormone-binding globulin (SHBG) levels are elevated in KS (18). More than 90% of men have increased levels of serum gonadotropins, particularly FSH, because inhibin-B levels are low in individuals with KS (5). Because of low androgen levels, individuals with KS can have low bone mineral density and are at increased risk of developing osteoporosis, despite seemingly adequate androgen
Clinical Characteristics of Men With Klinefelter's Syndrome
Small testes 99-100
Elevated gonadotropins 90-100
Low testosterone levels 65-85
Reduced facial and pubic hair 50-80
therapy (20). This may result from the failure to achieve peak bone mass early in life, because testosterone replacement before the age of 20 can improve bone mass to normal levels, whereas testosterone therapy started later in life has a less potent effect (21). As a result, calcium and vitamin D supplementation, as well as baseline densitometry, are probably prudent in individuals with KS, especially those who began androgen therapy later in life.
At one time, individuals with KS were believed to be frequently retarded and/or at increased risk of criminal behavior (22,23). Those studies were often misleading, because they were based on preselected (usually committed or incarcerated) populations; however, such populations were not representative of the syndrome as a whole. Subsequent population-based studies have demonstrated a nonsignificant, but slightly increased, rate of incarceration among individuals with KS. The increased rate of imprisonment is most likely accounted for by a lower average score on IQ tests when compared to controls (24).
When tested, groups of adult individuals with KS do exhibit significant deficits in language-processing skills, including reading and spelling, verbal processing speed, verbal and nonverbal executive abilities, and motor dexterity (25,26). In general, this leads to lower average school performance and an increased frequency of psychological consultation. In addition, adolescent males with KS exhibit lowered sexual activity compared with their peers (27). It is important to remember that individual variation in mental function is marked; some individuals with KS perform well above average on intelligence tests. Moreover, it seems likely that early developmental interventions and language tutoring in boys can assist in preventing disabling difficulties with language skills later in adult life (28,29).
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