Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome

Abstract

Paternal origin of the supernumerary X chromosome is associated with later onset of puberty and longer CAG repeats of the AR with later pubertal reactivation of the pituitary-testicular axis in KS boys. Identifying genetic factors that affect the phenotype may lead to a better understanding of the pathogenesis of KS.

Testicular Function in Klinefelter Syndrome

“…In another study, however, the only parameter associated with CAG repeat length was penile length; the correlation was inverse [63]. In addition, KS boys with a longer CAG repeat show later onset and slower progression of puberty and slower testicular degeneration process [60]. These findings are in agreement with diminished AR response to androgens when the AR gene has a longer CAG repeat.…”

“…The supernumerary X chromosome is paternal in 40–60% and maternal in 40–60% of KS cases [3, 7, 59]. In our study of 14 adolescent KS boys, the 3 subjects with an additional paternal X chromosome showed later onset and slower progression of puberty [60]. Other studies [61,62,63] have, however, suggested that parental origin of the extra X chromosome has no evident effect on the phenotypes of KS males.…”

“…Other studies [61,62,63] have, however, suggested that parental origin of the extra X chromosome has no evident effect on the phenotypes of KS males. Data from several small patient series suggest that X chromosome isodisomy/heterodisomy and X chromosome inactivation pattern have no impact on the phenotype [60, 62, 63], although these issues require study in detail in larger patient series.…”

Presence of spermatogonia in 47,XXY men with no spermatozoa recovered after testicular sperm extraction

“…Multiple genetic mechanisms may explain this phenotypic variability, all related to the presence of a supernumerary X chromosome. The excessive dosage of X-linked genes that escape inactivation, skewed X-inactivation, and the parental origin of the supernumerary X chromosome may all influence the phenotypical characteristics of men with KS (23)(24)(25)(26). Because 10% of protein-encoding genes on the X chromosome are testis-specific, it is not surprising that testicular function is affected in men with KS (5).…”

“…Inactivation of the excessive X chromosome(s) occurs in men with KS, but increased expression of genes located on the X chromosome that escape inactivation might play an important role. It is assumed that 15% of X-linked genes escape inactivation (26). It is, however, not clear whether the abnormal karyotype affects the germ cells or rather the somatic niche cells.…”