(73/226) Prosthetic valve endocarditis due to Neisseria elongata subsp. elongata in a patient with Klinefelter's syndrome.

A case is reported of prosthetic valve endocarditis due to Neisseria elongata subsp. elongata in a patient with Klinefelter's syndrome. This is believed to be only the third case of endocarditis reported due to this subspecies. N. elongata is difficult to identify, and is morphologically and biochemically similar to Kingella spp. Sequencing of the 16S rRNA gene is useful for identification. The patient was successfully treated with amoxicillin and gentamicin, followed by ceftriaxone.  (+info)

(74/226) Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene: case report.

Patients with Klinefelter syndrome (47,XXY) are characterized by eunuchoid body proportions, gynaecomastia, small firm testes and azoospermia. We describe a Klinefelter patient (non-mosaic 47,XXY karyotype) who was heterozygous for the classical 1138G>A mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, which is a gain-of-function mutation resulting in achondroplasia. The patient had phenotypic characteristics of achondroplasia (e.g. short limbed dwarfism and frontal bossing). Testicular volume was 8 ml at 27 years of age and repeated semen samples showed sperm concentrations of 0.175 million/ml. Serum FSH levels were elevated (21.7 IU/l) compared to normal age-matched healthy male controls and patients with non-mosaic Klinefelter syndrome, and inhibin B levels were low-normal, in contrast to the usually undetectable inhibin B levels in adult Klinefelter patients. The patient fathered a child from a spontaneous pregnancy. The observed testicular size and function in our patient contrast the typical findings in classical Klinefelter syndrome. We speculate that the alteration of FGFR3 protein function in our Klinefelter patient alleviated the destruction of the seminiferous tubules and may suggest that the fibroblast growth factor family has a pleiotrophic function in human spermatogonia, which physiologically express FGFR3.  (+info)

(75/226) A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene.

Due to the high prevalence and variable phenotype of patients with Klinefelter syndrome, there is a need for a robust and rapid screening method allowing early diagnosis. Here, we report on the development and detailed clinical validation of a quantitative real-time PCR (qPCR)-based method of the copy number assessment of the androgen receptor (AR) gene, located to Xq11.2-q12. We analysed samples from 50 individuals, including a healthy male and female controls and patients with Klinefelter syndrome (47,XXY; 48,XXXY) (n = 28), mosaicisms (46,XX/47,XXY/48XXYY; 45,X/46,XY) (n = 3), other sex chromosome abnormalities (46,XX males; 47,XYY)(n = 4) and normal karyotypes (46,XY) (n = 13). The reference range for the AR-copy number was established as 0.8-1.2 for one copy and 1.7-2.3 for two copies. The qPCR results were within the reference range in 17/18 samples (94%) or 30/31 (97%) samples with one or two copies of the AR gene, respectively. None of the Klinefelter patients were misdiagnosed as having a karyotype with only one X-chromosome, and in none of the 46,XY males were two copies demonstrated. We systematically compared qPCR results with those obtained with another PCR-based method, the XIST-gene expression. The XIST-expression based assay was correct in only 29/36 samples (81%). Our findings demonstrated that the AR-qPCR technique is a simple and reliable screening method for diagnosis of patients with Klinefelter syndrome or other chromosomal disorders involving an aberrant number of X-chromosomes.  (+info)

(76/226) High normal testosterone levels in infants with non-mosaic Klinefelter's syndrome.

OBJECTIVE: Klinefelter's syndrome (KS) is associated with hypergonadotrophic hypogonadism in adulthood. However, limited information exists about the age at which hypogonadism occurs. The hypothalamic-pituitary-gonadal (HPG) axis is transiently activated during the first months of life, offering the opportunity to study testicular function by spontaneous, basal hormone levels. The aim of this study was to evaluate the HPG axis in KS infants. DESIGN: Cross-sectional study. METHODS: Ten KS infants aged 3.1 months (range 1.8-3.8) and 613 healthy controls aged 3.0 months (range 2.0-4.5). Serum levels of total and free testosterone (T), LH, FSH, inhibin B and sex hormone-binding globulin (SHBG) were determined. RESULTS: KS infants had significantly higher concentrations of total T (5.0 (2.2-11.2) vs 3.4 (0.7-8.3) nmol/l, P = 0.02), free T (31.6 (18.2-61.8) vs 22.1 (4.3-48.4) pmol/l, P = 0.01), LH (3.3 (1.3-4.6) vs 1.7 (0.6-4.3) IU/l, P = 0.005) and FSH (1.7 (1.1-4.1) vs 1.2 (0.4-3.0) IU/l, P = 0.007) than controls. SHBG and inhibin B did not differ from controls. LH/T and LH/free T ratios were normal, whereas the FSH/inhibin B ratio was elevated (6.5 (2.7-16.9) vs 3.0 (0.78-11.4), P = 0.005) when compared to controls. The majority of KS infants had normal bivariate hormonal combinations. CONCLUSION: We found increased FSH/inhibin B ratio as a possible sign of Sertoli cell dysfunction. However, serum levels of T were high normal suggesting an altered pituitary-gonadal set point.  (+info)

(77/226) Klinefelter's syndrome with unelevated serum gonadotropin levels (a case report).

Two cases of Klinefelter's syndrome with 47 XXY karyotype associated with unelevated follicular stimulating hormone (FSH) and luteinizing hormone (LH) levels are reported. The literature is briefly reviewed.  (+info)

(78/226) Mosaic tetrasomy 9p case with the phenotype mimicking Klinefelter syndrome and hyporesponse of gonadotropin-stimulated testosterone production.

Tetrasomy 9p is a rare clinical syndrome and about 30% of known cases exhibit chromosome mosaicism. The cases with tetrasomy 9p mosaicism have been reported to show the various phenotypes. On the other hand, Klinefelter syndrome is well recognized chromosomal abnormality caused by an additional X chromosome in males (47,XXY), and the characteristic clinical findings include tall stature, immaturity of external genitalia, testicular dysfunction. Here, we report a 10-year-old male with tetrasomy of 9p mosaicism, whose phenotypic feature is mimicking Klinefelter syndrome. He was referred to our hospital for inconspicuous penis. He showed tall height (+2.5 SD). Endocrinological examination revealed the poor testosterone response to human chorionic gonadotropin administration, which indicated the testicular hypofunction, whereas MRI revealed concealed penis as a cause of inconspicuous penis. Because of the phenotype mimicking Klinefelter syndrome, karyotype of his blood lymphocytes was analyzed, and an additional marker chromosome was detected in 6% of the investigated metaphases. Fluorescence in situ hybridization analysis revealed that the marker chromosome was an isochromosome 9p, which resulted in tetrasomy 9p. Chromosome analysis of buccal smear also showed mosaicism for two karyotypes: 5% of cells had the isochromosome of 9p, and the other cells showed normal. This case is the second case with tetrasomy 9p mosaicism mimicking Klinefelter syndrome phenotype in the world. Our case, together with previously reported cases with the same association, indicates the possibility of testicular hypofunction and urogenital anomalies induced by overexpression of some genes on chromosome 9p.  (+info)

(79/226) Routine screening for classical azoospermia factor deletions of the Y chromosome in azoospermic patients with Klinefelter syndrome.

AIM: To evaluate the occurrence of classical azoospermia factor (AZF) deletions of the Y chromosome as a routine examination in azoospermic subjects with Klinefelter syndrome (KS). METHODS: Blood samples were collected from 95 azoospermic subjects with KS (91 subjects had a 47,XXY karyotype and four subjects had a mosaic 47,XXY/46,XY karyotype) and a control group of 93 fertile men. The values of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. To determine the presence of Y chromosome microdeletions, polymerase chain reaction (PCR) of five sequence-tagged site primers (sY84, sY129, sY134, sY254, sY255) spanning the AZF region, was performed on isolated genomic DNA. RESULTS: Y chromosome microdeletions were not found in any of the 95 azoospermic subjects with KS. In addition, using similar conditions of PCR, no microdeletions were observed in the 93 fertile men evaluated. The level of FSH in KS subjects was higher than that in fertile men (38.2 +/- 10.3 mIU/mL vs. 5.4 +/- 2.9 mIU/mL, P < 0.001) and the testosterone level was lower than that in the control group (1.7 +/- 0.3 ng/mL vs. 4.3 +/- 1.3 ng/mL, P < 0.001). CONCLUSION: Our data and review of the published literature suggest that classical AZF deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KS subjects with a 47,XXY karyotype. In addition, routine screening for the classical AZF deletions might not be required for these subjects. Further studies including partial AZFc deletions (e.g. gr/gr or b2/b3) are necessary to establish other mechanism underlying severe spermatogenesis impairment in KS.  (+info)

(80/226) Is the prevalence of Klinefelter syndrome increasing?

The birth prevalence of sex chromosome trisomies (SCT), that is individuals with an XYY, XXY or XXX sex chromosome constitution, is traditionally based on six surveys of unselected newborns carried out in the 1960s and early 1970s. All three SCTs had a prevalence of 1 in 1000 same sex births. We re-examined these prevalences based on additional cytogenetic studies of newborn surveys, spontaneous abortions, perinatal deaths and prenatal diagnoses. The more recent newborn surveys suggest there has been an increase in the prevalence of XXYs, but not of the other two SCTs since the original newborn series. The prevalence of XXYs has risen from 1.09 to 1.72 per 1000 male births (P=0.023). We suggest that such an increase, in the absence of an increase in the prevalence of XXX, is unlikely to be due to increased maternal age. As XXY is the only chromosome abnormality known where a substantial proportion ( approximately 50%) arise as the result of non-disjunction at the first paternal meiotic division, we speculate that some factor may be interfering with pairing and/or recombination of the sex bivalent at the paternal MI division.  (+info)