(65/226) Atypical presentation of Prader-Willi syndrome with Klinefelter (XXY karytype) and craniosynostosis.

Prader-Willi syndrome is a mental retardation genetic disorder also characterized by hypogonadism, hyperphagia and obesity. We report on a four-years-old boy, born to consanguineous parents, with uncommon co-occurrence of Prader-Willi syndrome, 47,XXY karyotype (Klinefelter syndrome) and coronal craniosynostosis. These are different unrelated conditions and it was not described before in the same patient to the best of our knowledge.  (+info)

(66/226) Klinefelter syndrome and other sex chromosomal aneuploidies.

The term Klinefelter syndrome (KS) describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY) to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH). The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ) decrease of approximately 15-16 points, with language most affected, particularly expressive language skills.  (+info)

(67/226) Klinefelter's syndrome (karyotype 47,XXY) and schizophrenia-spectrum pathology.

Klinefelter's syndrome, characterised by a 47,XXY chromosomal pattern, has largely been associated with physical abnormalities. Here, we report high levels of schizophrenia-spectrum pathology in 32 men with this syndrome in comparison with 26 healthy controls. This may have implications for treatment of have implications for treatment of Klinefelter's syndrome and suggests that the X chromosome may be involved in the aetiology of schizophrenia.  (+info)

(68/226) Genetic and epigenetic risks of intracytoplasmic sperm injection method.

Pregnancies achieved by assisted reproduction technologies, particularly by intracytoplasmic sperm injection (ICSI) procedures, are susceptible to genetic risks inherent to the male population treated with ICSI and additional risks inherent to this innovative procedure. The documented, as well as the theoretical, risks are discussed in the present review study. These risks mainly represent that consequences of the genetic abnormalities underlying male subfertility (or infertility) and might become stimulators for the development of novel approaches and applications in the treatment of infertility. In addition, risks with a polygenic background appearing at birth as congenital anomalies and other theoretical or stochastic risks are discussed. Recent data suggest that assisted reproductive technology might also affect epigenetic characteristics of the male gamete, the female gamete, or might have an impact on early embryogenesis. It might be also associated with an increased risk for genomic imprinting abnormalities.  (+info)

(69/226) Seven pregnancies and deliveries from non-mosaic Klinefelter syndrome patients using fresh and frozen testicular sperm.

PURPOSE: The aim of this study was to investigate the feasibility of using frozen-thawed testicular sperm as well as the timing of testicular sperm extraction (TESE) in patients with non-mosaic Klinefelter syndrome. METHODS: Intracytoplasmic sperm injection (ICSI) was performed in six of 17 (35%) patients whose sperm was recovered by TESE. Multiple biopsies of both testes were performed on the day of oocyte retrieval in all but one of the six patients. RESULTS: Seven pregnancies and deliveries were achieved in five couples, and one couple was unsuccessful. Five pregnancies were achieved using fresh motile sperm, and two were achieved using frozen-thawed sperm. Sperm cryopreservation was not possible in one of the five couples because of the small number of recovered sperm, and possible in four other couples for subsequent ICSI. One woman whose husband had TESE performed prior to ovarian stimulation did not become pregnant. This may be due to the attainment of only a few immotile sperm following the frozen-thawed procedure. CONCLUSION: The outcome of ICSI using fresh or frozen-thawed testicular sperm in patients with non-mosaic Klinefelter syndrome was identical; however, TESE should be performed on the day of oocyte retrieval until such time as a procedure with a higher sperm yield from TESE is available. Moreover, an improved recovery procedure after cryopreservation-thawing of a single spermatozoon must be developed.  (+info)

(70/226) XXY (Klinefelter syndrome): a pediatric quantitative brain magnetic resonance imaging case-control study.

OBJECTIVE: An extra X chromosome in males (XXY), known as Klinefelter syndrome, is associated with characteristic physical, cognitive, and behavioral features of variable severity. The objective of this study was to examine possible neuroanatomical substrates of these cognitive and behavioral features during childhood and adolescence. METHODS: MRI brain scans were acquired for 42 XXY and 87 healthy XY age-matched control males. We compared these 2 groups on regional brain volumes and cortical thickness. RESULTS: Total cerebral volume and all lobar volumes except parietal white matter were significantly smaller in the XXY group, whereas lateral-ventricle volume was larger. Consistent with the cognitive profile, the cortex was significantly thinner in the XXY group in left inferior frontal, temporal, and superior motor regions. CONCLUSION: The brain-imaging findings of preferentially affected frontal, temporal, and motor regions and relative sparing of parietal regions are consistent with observed cognitive and behavioral strengths and weaknesses in XXY subjects.  (+info)

(71/226) Clinical report: a case of Williams Syndrome and Klinefelter Syndrome.

INTRODUCTION: Williams syndrome (WS) is a rare but well recognised neurodevelopmental disease affecting the connective tissue and the central nervous system. Many patients are identified through the presence of dysmorphic features and associated cardiac abnormalities. Klinefelter syndrome (KS) is associated with gynaecomastia, small testes, azoospermia and elevated gonadotropin levels. They are recognised in the second decade of life by their tall stature and delay in pubertal development. A combination of constitutive WS and KS has yet to be described. CLINICAL PICTURE: We report a child with these genetic aberrations, highlighting the clinical characteristics of such an individual. CONCLUSION: The manifestations and interactions of both conditions are also discussed.  (+info)

(72/226) Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.

Klinefelter's Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini-Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression-cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = -0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis.  (+info)