Early androgen deficiency in infants and young boys with 47,XXY Klinefelter syndrome.
ABSTRACT Klinefelter syndrome (KS) is characterized by the karyotype 47,XXY. In this study, we evaluated the physical and testicular failure phenotypes of infants and young boys with KS.
The evaluation included auxologic measurements, biologic indices of testicular function, and clinical assessment of muscle tone in 22 infants and young boys with KS, ages 1-23 months.
Mean length, weight, and head circumference in SDS were generally within the normal range at -0.3 +/- 1.0, -0.1 +/- 1.4, and 0.0 +/- 1.5, respectively. Mean penile length and testicular volume SDS were -0.9 +/- 0.8 and -1.1 +/- 0.8, indicating significantly reduced penile and testicular size. Mean testosterone levels for the boys < or =6 and >6-23 months were 128 +/- 131 (4.4 +/- 4.5 nmol/l) and 9.5 +/- 7.2 ng/dl (0.3 +/- 0.2 nmol/l), respectively. High-arched palate was observed in 6/17 boys and clinodactyly (5th finger) was observed in 15/16 boys. Hypotonia was evaluated clinically and was noted to be present in 12/17 boys.
The physical phenotype in infants and young boys with KS (1-23 months old) includes normal auxologic measurements and early evidence of testicular failure. Muscle tone was decreased in most of the boys. Testicular volume and penile length were diminished, indicating early androgen deficiency. The neonatal surge in testosterone was attenuated in our KS population. Thus, infants and young boys with KS have evidence of early testicular failure. The etiology of this failure and the clinical role of early androgen replacement require further study.
Article: Fragile X-related element 2 methylation analysis may provide a suitable option for inclusion of fragile X syndrome and/or sex chromosome aneuploidy into newborn screening: a technical validation study.[show abstract] [hide abstract]
ABSTRACT: Purpose:We show that a novel fragile X-related epigenetic element 2 FMR1 methylation test can be used along with a test for sex-determining region Y (SRY) to provide the option of combined fragile X syndrome and sex chromosome aneuploidy newborn screening.Methods:Fragile X-related epigenetic element 2, SRY, and FMR1 CGG repeat analyses were performed on blood and saliva DNA, and in adult and newborn blood spots. The cohort consisted of 159 controls (CGG <40), 187 premutation (CGG 56-170), and 242 full-mutation (CGG ~200-2,000) males and females, 106 sex chromosome aneuploidy individuals, and 151 cytogenetically normal controls.Results:At the 0.435 threshold, fragile X-related epigenetic element 2 analysis in males was robust on both blood DNA and newborn blood spots, with specificity and sensitivity of ~100% for full-mutation genotype. In females, the specificity was 99%, whereas half of full-mutation females were above the 0.435 threshold in both blood DNA and newborn blood spots. Furthermore, at this threshold, the test could not differentiate individuals with Klinefelter syndrome from female controls without using the SRY marker. When combined with SRY analysis, the test was consistent with most results for sex chromosome aneuploidies from karyotyping.Conclusion:Setting specific thresholds for fragile X-related epigenetic element 2 analysis and including the SRY marker provides the option to either include or exclude detection of sex chromosome aneuploidies as part of fragile X syndrome newborn screening.Genet Med advance online publication 11 October 2012Genetics in Medicine (2012); doi:10.1038/gim.2012.134.Genetics in medicine: official journal of the American College of Medical Genetics 10/2012; · 3.92 Impact Factor
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ABSTRACT: Klinefelter syndrome (KS) is associated with male infertility, hypogonadism, and learning disability. Morbidity and mortality are increased and the causes behind remain unknown. Is it the chromosome aberration or is it caused by postulated poorer socioeconomic status? The aim of the study was to study the socioeconomic profile in KS and the impact of these factors on mortality. This was a register study using Danish nationwide registries. One thousand forty-nine KS men and 100,824 controls were included. Information concerning cohabitation, fatherhoods, level of education, income, retirement, and death were obtained. Two hundred four KS and 14,725 controls died during the study period. For the socioeconomic parameters, median age at first relevant episode was calculated. Cohabitation, fatherhood, educational level, and retirement were analyzed using Cox regression, and income was analyzed using conditional logistic regression. Both analyses using each case and his matched controls as one stratum. KS men had significantly fewer partnerships [hazard ratio (HR) 0.66] and entered them later (median age 27.1 vs. 24.6 yr), fewer fatherhoods (HR 0.24),and they occurred later (median age 32.0 vs. 27.0 yr), lower educational level (HR 0.27), and lower income and were retired at an earlier age (43.5 vs. 60.3 yr). Mortality among KS men was significantly increased (HR 1.9), and after adjustment for cohabitation and educational status, mortality was still significantly increased (HR 1.5). A severely inferior outcome in all investigated socioeconomic parameters compared with the background population was present and mortality was increased and may partially be caused by the poorer socioeconomic status.The Journal of clinical endocrinology and metabolism 05/2011; 96(7):2098-104. · 6.50 Impact Factor
The Journal of clinical endocrinology and metabolism 02/2013; 98(2):31A-2A. · 6.50 Impact Factor