Klinefelter s syndrome

Down s syndrome Bloom s syndrome Fanconi s anemia Klinefelter s syndrome Ataxia telangiectasia Langerhans cell histiocytosis Shwachman s syndrome Severe combined... 

The influence of genetics in leukemia is supported by several observations. For example, among identical twins, the occurrence of ALL is associated with a 20% to 25% chance of the disease developing in the other twin within 1 year. In fraternal twins, there is a fourfold increase in the risk of leukemia compared with the normal population. Additionally, leukemia is known to be increased in several chromosomally abnormal populations. Patients with Down s syndrome have a 20 times increased risk of developing leukemia compared with the rest of the population. Patients with Klinefelter s syndrome and Bloom s syndrome also have an increased incidence of leukemias.7... 

Klinefelter s Syndrome This condition affects males where there are 3 chromosomes, XXY, instead of XY in the sex chromosome. These males are normally infertile and have some female characteristics. There may be a greater risk in developing germ cell tumors. 

Hereditary hemorrhagic telangiectasia" Moyamoya syndrome Klinefelter s syndrome Progeria... 

The ability of androgens to counter osteoporosis is the basis of their use as a supplement to estrogens in one version of hormone replacement therapy. Testosterone can increase markers of bone formation (43). However, the early closure of epiphyses, with an arrest of growth, is a risk if children are exposed to these substances this latter effect may be produced by the estrogen to which testosterone is metabolized. In some patients with excessive growth (such as Klinefelter s syndrome or Marfan syndrome) the effect is exploited therapeutically (SEDA-21, 434). Follow-up in these subjects at the age of 21-30 years showed no abnormalities of testicular function as a consequence of treatment. 

Klinefelter s syndrome (47, XXY) and mosaics Autosomal and sex chromosomes, polyploidies True hermaphroditism Defective androgen biosynthesis... 

Decreased concentrations of 17-KSs usually are found in men with primary hypogonadism (Klinefelter s syndrome and castration), in secondary hypogonadism (panhypopituitarism), and in women with pituitary hypoadrenahsm (Addison s disease). Increased concentrations are found in patients with testicular tumors (interstitial cell tumor and chorioepithelioma), adrenal hyperplasia, and adrenal carcinoma, and in some women with hirsutism. 

The sex chromosome composition of human males and females is XY and XX, respectively. If cells contain more than one X chromosome, all except one are inactivated. The cells of XX females contain a structure called a Barr body, which is a condensed, heterochro-matic, transcriptionally inactive X chromosome. The cells of XXY males also contain a Barr body. XXY males suffer from Klinefelter s syndrome they are usually mentally retarded, sterile, and suffer from physiological and developmental abnormalities. It is thought that extra X chromosomes must be prevented from gene expression to preserve the correct gene dosage in both males and females. 

Autosomal trisomy A male with Klinefelter s syndrome Sex chromosome aneuploidy A female with Turner s syndrome Sex chromosome triploidy... 

The answer is b. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 57—84. Wilson, pp 123-148.) The recurrence risk for aneuploidies caused by meiotic nondisjunction is about 1% in addition to the maternal age-related risk. It is not known why the risk for aneuploidy increases slightly after an affected child is born, but parental karyotypes are almost always normal. Surveys of penal institutions have revealed an increased incidence of 47,XYY individuals, but other conditions with mental disability are increased as well. As with other chromosomal syndromes, the phenotype of 47,XYY is variable and can be found coincidentally in normal males. It would therefore be inappropriate to label a child as abnormal in school unless there have been previous concerns about a medical disorder. Males with Klinefelter s syndrome (47,XXY), rather than those with 47,XYY syndrome, are often sterile and may require supplementation with male hormones. 

The answer is e. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 57-84. Wilson, pp 123-148.) Children with chromosome abnormalities often exhibit poor growth (failure to thrive) and developmental delay with an abnormal facial appearance. This baby is too young for developmental assessment, but the catlike cry should provoke suspicion of cri-du-chat syndrome. Cri-du-chat syndrome is caused by deletion of the terminal short arm of chromosome 5 [46,XX,del(5p), also abbreviated as 5p—] as depicted in panel e. When a partial deletion or duplication like this one is found, the parents must be karyotyped to determine if one carries a balanced reciprocal translocation. The other karyotypes show (a) deletion of the short arm of chromosome 4 [46,XY,del(4p) or 4p—] (b) XYY syndrome (47,XYY) (c) deletion of the long arm of chromosome 13 [46,XX,del(13q) or 13q-] (d) Klinefelter s syndrome (47,XXY). Most disorders involving excess or deficient chromosome material produce a characteristic and recognizable phenotype (e.g., Down s, cri-du-chat, or Turner s syndrome). The deletion of 4p- (panel A) produces a pattern of abnormalities (syndrome) known as Wolf-Hirschhorn syndrome deletion of 13q- produces a 13q— syndrome (no eponym). The mechanism(s) by which imbalanced chromosome material produces a distinctive phenotype is completely unknown. 

Other genetic syndromes sometimes associated with diabetes Down s syndrome Klinefelter s syndrome Turner s syndrome Wolfram s syndrome Friedreich s ataxia Huntington s chorea Laurence-Moon-Bieldel syndrome Myotonic dystrophy Porphyria... 

Patients with Klinefelter s syndrome have serum alkaline phosphatase levels appropriate to their age (H24). 

Inherited disorders such as Klinefelter s syndrome (a 47 XXY karyotype). 

Klinefelter s Syndrome. In trisomy, there is a diploid set of homologous chromosomes plus one extra chromosome. Geneticists have classified the chromosomes according to their size and shape, and each chromosome is referred to by a number. The most classical example of trisomy is mongolism, which is believed to result from nondisjunction in the mother. In mongolism, the oocyte contains two 21 chromosomes. (The type of trisomy is referred to by the number of the chromosome that is trisomic, usually using the new international standard nomenclature for example, in mongolism the type of trisomy is trisomy 21). After fertilization, each cell of the embryo contains three chromosomes, 21, two derived from the oocyte and one from the spermatocyte. 

Trisomy XXY leads to the development of Klinefelter s syndrome in males (see Fig. 8-24). 

The presence of the Y chromosome determines the differentiation of the primitive embryonic gonad into testes. Its presence, in addition to two X chromosomes (47 chromosomes instead of 46), is responsible for the development of sexual ambivalence (Klinefelter s syndrome). But we shall see that the syndrome also occurs in patients with different karyotypes. These phenotypically male individuals have small testicles with agenesis and sometimes hyalinization of the seminiferous tubules. In contrast, foci of hyperplasia of the Leydig cells are found. 

The victims of this chromosomal anomaly are often mentally retarded and sterile. The levels of urinary gonadotropins are usually high in patients with Klinefelter s syndrome, but those of 17-ketosteroids are decreased. Examination of sex chromatin is always positive. The syndrome is not rare—it has been reported in 1 of 400 newborns. Although in the typical Klinefelter syndrome, the karyotype is XXY, the syndrome has also been observed in patients with 48 chromosomes (48XXYY or 48 XXXY) and 49 chromosomes (49XXXYY or 49XXXXY). 

As in many chromosome anomalies, patients with Klinefelter s syndrome present mosaicism, or the presence of cells with different karyotypes in the same individual. Since all cells of the body descend from the fertilized egg, it can be expected that in the normal person all cells will have the same karyotype. This is not the case in patients with chromosomal disorders. In these patients, some cells may have a normal karyotype of the male or female, while others have an abnormal karyotype. Twenty percent of patients with Klinefelter s syndrome exhibit mosaicism. 

Fig. 8-24. Giemsa-banded karyotype with 47 chromosomes and 3 sex chromosomes, the usual pattern observed in the Klinefelter s syndrome. (From R. Sparkes)...

Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter s syndrome. Lancet. 2004 364(9430) 273—283. 

Scofield RH, Bruner GR, Namjou B, et al. Klinefelter s syndrome (47, XXY) in male systemic lupus erythematosus patients support for the notion of a gene—dose effect from the X chromosome. Arthritis Rheum. 2008 58(8) 2511—2517. 

Sawalha AH, Harley JB, Scofield RH. Autoimmunity and Klinefelter s syndrome when men have two X chromosomes. / Autoimmun. 2009 33(l) 31-34. 

Sex in animals is determined by the distribution of the special X and Y sex chromosomes in the progeny. In most species an XX combination determines the female sex and an XY combination the male. In some inborn anomalies of sex development which have been thoroughly studied in man (Klinefelter s syndrome, Turner s syndrome, and so on), as a result of failure of the chromosomes to separate, individuals wifli anomalous sets of sex chromosomes are formed (XXY, XXXY, XXX, XXXX, XXXXX, and XXXXY). In all cases with an increase in the number of X chromosomes, the supernumerary X chromosomes were found to be of the late replicating type (Grumbach et al., 1963 Rowlyetal., 1963 Atkins et al., 1963). The number of X-chromosomes with late replication in every case was one less than the total number of X-chromo-somes, and it was on account of these chromosomes that the sex chromatin of the interphase nucleus was formed. On the basis of these facts the hypothesis was put forward (Hsu, 1964a Taylor, 1964) that late replication of DNA in the chromosomes correlates or is directly connected with... 

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