Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome.
OBJECTIVE
To investigate how genetic features of the X chromosome influence growth, pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome (KS). Previous studies have suggested that genetic features of the X chromosome may contribute to the wide phenotypic variation in KS.


METHODS
A prospective clinical study.


METHODS
Fourteen nonmosaic 47,XXY boys, aged 10-13.9 years.


METHODS
The relationship of genetic features of the X chromosome, including parental origin of X chromosomes, the CAG repeat length of the androgen receptor (AR) gene, and X inactivation with progression of pubertal development, growth and testicular function in KS boys.


RESULTS
Paternal (47,XmXpY, n = 3) as compared to maternal (47,XmXmY, n = 11) origin of the supernumerary X chromosome was associated with a later onset of puberty. In 47,XmXpY patients, serum LH concentrations increased above 1.0 IU/l at 12.5 +/- 0.6 years (mean +/- SD), Tanner stage P2 occurred at 12.5 +/- 0.7 years, and pubertal acceleration of growth was noted at 13.9 +/- 1.4 years and peak velocity at 14.5 +/- 0.8 years. All of these occurred 1.3-1.9 years later than in 47,XmXmY patients (P = 0.01-0.09). In 47,XmXmY subjects, CAG repeat length (range 17-26) correlated with age at which serum LH level first exceeded 1.0 IU/l (rs = 0.63, P = 0.06, n = 10) and testosterone 1.0 nmol/l (28.8 ng/dl) (rs = 0.78, P = 0.02, n = 10).


CONCLUSIONS
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.
Wikström
Anne M
AM
Hospital for Children and Adolescents, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland. anne.wikstrom@fimnet.fi
Painter
Jodie N
JN
Raivio
Taneli
T
Aittomäki
Kristiina
K
Dunkel
Leo
L
D000293:Adolescent; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D018392:Genomic Imprinting; D006801:Humans; D007713:Klinefelter Syndrome / Q000235:genetics* / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D010641:Phenotype; D011446:Prospective Studies; D011627:Puberty; D011944:Receptors, Androgen / Q000235:genetics; D013737:Testis / Q000473:pathology* / Q000503:physiopathology; D018911:Trinucleotide Repeats; D049951:X Chromosome Inactivation
D011944:Receptors, Androgen