One of the largest studies, sponsored by the National Institute of Child Health and Human Development (NICHD), looked at chromosomes of over 40,000 babies (NICHD 2003).
Today the syndrome is defined as "the spectrum of phenotypic features resulting from a sex chromosome complement that includes two or more X chromosomes and one of more Y chromosomes (Mandoki et al, 1991).
DESCRIPTION OF THE SYNDROME.
1. Pathophysiology and Genetics.
The addition of an extra chromosome (either X or Y) in a male's XY normal genotype causes different physical and mental abnormalities. The greater the number of extra X chromosomes a person has, the more extensive the physical and mental abnormalities are (De La Chapelle 1990). For example, as the number of X chromosomes increases, the affected person suffers from a greater number of abnormalities in heart, bones, testicles, intelligence quotient (IQ) and even in their ability to speak or understand.
About 50-60% of Klinefelter syndrome cases is due to "maternal nondisjunction- (failure of chromosomes to pair properly during meiosis and exchange genetic material) (for proper definition see Glossary). The remaining causes are due to paternal nondisjunction (Chen 2003). The most common karyotype (genetic profile) is 47,XXY (about 80-90% of all cases). In a few cases there are other sex-chromosomal abnormalities, which have physical characteristics (phenotype) similar to Klinefelter, and are called often variants of Klinefelter. Mosaicism (mix of different genetic combinations like 46,XY/47,XXY) can be seen in about 10% of cases. Other various karyotypes, including 48,XXYY, 48,XXXY, 49,XXXYY, and 49,XXXXY, are rare (Ferrier et al, 1974; Peet et al, 1998; Robinson et al, 1979; Zaleski et al, 1966). The chromosomal abnormalities and the syndromes arising from those abnormalities are shown in Figure 1 (McGehee et al, 1976). A list of sex-chromosome related syndromes is seen in Table 1 (McGehee et al, 1976).
