Klinefelter syndrome

Klinefelter syndrome (47,XXY) is seen in approximately 1 in 1,000 males (all individuals with this condition have a male phenotype because they have a Y chromosome). Klinefelter males are nearly always sterile because of atrophy of the seminiferous tubules. They tend to be taller than average, with abnormally long arms and legs. Breast development (gynecomastia) is seen in about one third of cases, and the IQ is on average 10-15 points below that of unaffected siblings. Individuals have also been seen with 48.XXXY and 49,XXXXY karyotypes the additional X chromosomes produce a more severely affected phenotype. 

Primary hypogonadism (congenital or acquired) Test cu ar failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. 

In men testosterone administration is indicated for primary hypogonadism, e.g. in Klinefelter syndrome or after orchidectomy, and for hypopituitarism. 

Klinefelter syndrome In humans, a genetically determined condition in which the individual has two X and one Y chromosome. Affected individuals are male and typically tall and infertile. 

Santarelli, L., Gabrielli, M., Orefice, R., Nista, E.C., SerriccMo, M., Nestola, M., Rapaccini, G., de Ninno, M., Pola, R, Gasbarrini, G., Gasbarrini, A. Association between Klinefelter syndrome and focal nodular hyperplasia. J. Clin. Gastroenterol. 2003 37 189-191... 

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). 

Arsenic exposure was associated with Klinefelter syndrome (2/30). The cytogenetic study in blood was however carried out on a small sample size of 30 arsenic-exposed subjects in Ballia District, UP, India, where maximum concentration of arsenic was reported to be around 0.37 ppm in drinking water [19 ]. 

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... 

Aneuploidy in live births and abortions arises from aneuploid gametes during germ cell meiosis. Trisomy or monosomy of large chromosomes leads to early embryonic death. Trisomy of the smaller chromosomes allows survival but is detrimental to the health of an affected person, for example, Down s syndrome (trisomy 21), Patau syndrome (trisomy 13) and Edward s syndrome (trisomy 18). Sex chromosome trisomies (Klinefelter s and XXX syndromes) and the sex chromosome monosomy (XO), known as Turner s syndrome, are also compatible with survival. 

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). 

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