Klinefelter's Syndrome - Report Example

Klienfelters Syndrome is the most frequent form of abnormal sex chromosome. Major Klienfelters Syndrome people typically have XXY syndrome and is characterized by 47,XXY genotype. The spontaneous mistake during the division of the sex chromosomes in either the egg or the sperm i.e. chromosome nondisjunction is responsible for the introduction of two or more copies of the X chromosome instead of the usual one copy. This genetic abnormality shows gender difference and is most prevalent in male population among all ethnic groups. The male patients with 47,XXY genotype in all their cells usually are sterile, while the individuals exhibiting mosaicism (46,XY/47,XXY) are fertile. This is not hereditary disorder therefore, risk factors for having a child that carries the extra chromosome are absent. The chronological order of personal development including physical, language and social progress is hampered in this chromosomal disorder. The number and distribution of cells containing the extra sex X chromosome in the body, decides the extensiveness and seriousness of syndrome. The Klienfelters Syndrome phenotype is variable, but it is generally associated with hypogonadism, androgen deficiency and infertility. Keywords Klinefelter syndrome; XXY syndrome; 47,XXY genotype; sex chromosomal disorder; chromosome nondisjunction; mosaic pattern; 46,XY/47,XXY; hypogonadism; infertility Introduction Klinefelter’s Syndrome (KS) is relatively common condition characterized by uncommon number of X and/or Y chromosomes in most of their cells. The term Klinefelter syndrome (KS) is also referred as XXY syndrome due to introduction of an additional X chromosome in the cell. KS is named after an American physician Harry F. Klinefelter who invented and reported this ailment. He found out nine male cases having enlarged breasts, sparse facial and body hair, small testes, and an inability to produce sperm (Bock, 1993). Klinefelter’s Syndrome (KS) is a genetic disorder that mainly occurs in male gender in all ethnic groups. KS leads to gonosomal aberration in men (Kamischke, 2003). This most commonly includes hypogonadism, androgen deficiency and infertility (Van Rijn, Aleman, Swaab, & Kahn, 2006). Genetics Human beings have complete set of 46 chromosomes, in which 22 pairs of non-sex determining chromosomes called autosomes and a pair of sex chromosome. Humans have X and Y sex chromosomes, a pair of X chromosomes (in females) and a pair containing a X and a Y chromosome (in males). Genes which are located on the chromosomes have a specific role to perform. Genes on X chromosomes mark out female characteristics and genes on Y chromosomes mark out male features. The individual suffering from KS has abnormal male karyotype containing at least one extra X chromosome. This results in the karyotype of 47, XXY.  Figure 1 shows the chromosome picture (karyotype) from a male with XXY Syndrome (Barlow-Stewart, 2007). Figure 1: Chromosome picture (karyotype) from a male with XXY Syndrome (Barlow-Stewart, 2007) Other less frequent variants of KS include 48, XXYY; 48, XXXY and 49, XXXXY. This is very common genetic abnormality which makes affected individual, neither male nor female. Inheritance Genes positioned on the sex chromosomes are responsible for unique inheritance patterns. During normal fertilization, the male sperm fuses with the female egg and give rise to the embryonic cells. X chromosome comes from the egg and every sperm gives either a X or a Y chromosome. The normal cells contain 46 chromosomes with XY genotype for male fetus while, 46 chromosomes with XX genotype for female fetus. The fault in the process of fertilization leads to KS. During faulty fertilization, the male sperm fuses with the female egg and give rise to the daughter cells bearing at least one extra chromosome. The arrival of excess X chromosome is either from a sperm or an egg. This is explained in Figure 2 (Barlow-Stewart, 2007). Figure 2: When the egg has 24 chromosomes, and the sperm has the usual 23, the baby’s cells will contain 47 chromosomes instead of 46. This may also happen in the reverse situation. During the first or second division of gametogenesis, chromosome omits the detachment step leading to meiotic nondisjunction and unwanted entry of additional X chromosome into the cell. Also, mitotic nondisjunction in the developing zygote may cause abnormal geneotype with surplus X chromosome. The reasons for this faulty cell division are unknown. The cells of KS individuals contain minimum 47chromosomes (Visootsak & Graham, 2003). Age increases the possibility of KS in older women while conceiving because X chromosome nondisjunction elevates with progressing age. The same age risk factor does not exist in men. Since, this chromosomal abnormality occurs as an accident in the egg or sperm, it is not a hereditary disorder. Therefore, KS is not passed from the parents to their offspring (Hammett, 1998). In some cases of KS, same person has two populations of cells with different genotypes. This is referred as a mosaic pattern of cells. In some body parts the cells possess normal 46 chromosomes with XY genotype, while other parts possess abnormal 47 chromosomes with XXY genotype. The KS individuals exhibiting mosaicism (46, XY/47, XXY), possessing some normal male karyotype cells, are able to produce sperm and progeny, whereas the non-mosaic males are sterile, that is, they are unable to produce sperm and offspring (Hammett, 1998). Mosacism is shown by only 6% of KS males having XXY syndrome (Barlow-Stewart, 2007). Sometimes, at the time of paternal meiosis, Y material including sex determining region (SRY) is translocated to give rise to daughter cells having 46,XX males (Visootsak & Graham, 2006). It was reported that when 113 embryos from couples with Klinefelters syndrome were compared with 578 embryos from control couples with X-linked disease, increased risk (54%) of abnormal embryos was seen in KS couples. Therefore, non-mosaic KS couples are warned about the abnormal embryos (Staessen, 2003). Incidence The abnormal karyotype of 47, XXY is present in a male population with an incidence of 1:600 male newborns (Kamischke, 2003) while other variants like 48,XXYY; 48,XXXY and 49, XXXXY are present rarely, in 1 per 50,000 male births (Visootsak & Graham, 2003). More than 60% of the cases of 47, XXY are the karyotype from blood. KS disorder is the leading cause of endocrine, psychiatric, or infertility problems (Smyth & Bremner, 1998). The number and distribution of cells containing the extra sex X chromosome in the body, decides the extensiveness and seriousness of syndrome. The rare cases having 48, XXYY; 48, XXXY and 49, XXXXY exhibits farther complications than usual XXY syndrome. Phenotypic characteristics This aneuploidy (abnormal number of chromosomes) in KS gives rise to variable phenotypic characteristics in individuals including altered physical and psychological traits. Altered developmental milestones may be observed in patients suffering from KS. Generally, the variants of KS other than XXY syndrome may result in a more abnormal phenotype. Physical Characteristics The consistent significant physical characteristics in KS affected individuals include small testicular size with elevated gonadotropins, longer arms and legs. The variable features include impaired secondary sexual characteristics like gynecomastia (breast development), eunuchoid body habitus and sparse body hair in about 56% to 88% population (Visootsak & Graham, 2003). This impairment is due to decrease in androgen production (testosterone). The normal adolescent associated testicular growth is arrested. Motor development retardation like delay in walking might be observed in two thirds of KS cases. Psychological Characteristics The consistent significant behavioral characteristics in KS affected individuals include specific impairments in verbal skills, a frequent occurrence of dyslexia and social dysfunctioning (Van Rijn, Aleman, Swaab, & Kahn, 2006). Overall Intelligence Quotient or IQ tends to be lower due to delayed progress in language and verbal skills. These disabilities may make them quiet, sensitive, and unassertive. In the exaggerated variants of KS cases, moderate to severe mental retardation and diminishing mental capacity can also be seen. Increase in number of X chromosomes impairs somatic and cognitive development. Other Complications KS also increases the risk of cardiovascular diseases, autoimmune diseases and breast cancer in males (Kathryn, 2005). References Barlow-Stewart, K. (2007). Klinefelter Syndrome: XXY Syndrome. Factssheet, 31. Bock, R. (1993) Understanding Klinefelter Syndrome:A Guide for XXY Males and Their Families. NIH Pub. No. 93-3202. Chen, H. (2007). Klinefelter Syndrome. emedicine form Web MD. Hammett, S. (1998). What is Klinefelters Syndrome (KS). Klinefelter organisation . Smyth, C., & Bremner, W. (1998). Klinefelter Syndrome. Arch Intern Med, 158(12):1309-1314. Staessen, C., Tournaye, H., Van Assche, E., Michiels, A., Van Landuyt, L., Devroey, P., Liebaers, I., & Van Steirteghem, A. (2003). PGD in 47,XXY Klinefelters syndrome patients. Hum Reprod Update, 9(4):319-30. Kamischke, A., Baumgardt, A., Horst, J. & Nieschlag, E. (2003). Clinical and Diagnostic Features of Patients With Suspected Klinefelter Syndrome, Journal of Andrology, 24 (1): 41-48. Kathryn, L. (2005). Klinefelter Syndrome National Library for Health, Specialist Libraries, Clinical Genetics. National Library for Health. Retrieved on 2007-04-07. Van Rijn , S., Aleman, A., Swaab, H., & Kahn, R. (2006). Klinefelter’s syndrome (karyotype 47,XXY) and schizophrenia-spectrum pathology. The British Journal of Psychiatry, 189: 459-461. Visootsak, J., & Graham, J. (2003). Klinefelter Syndrome and Its variants. Orphanet encyclopedia, http://www.orpha.net/data/patho/GB/uk-KS.html. Visootsak , J. & Graham, J. (2006). Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare Dis, 1:42. Read More