Although the effects of additional X and Y chromosomes tend to occur within characteristic domains, one of the most striking aspects of the SCAs is the heterogeneity in the degree to which the phenotypes are expressed. For example, while IQ may be depressed on average within males or females with an additional X chromosome, some individuals may be very high functioning and have an above average IQ, while others may have severe cognitive impairments [Ratcliffe, 1994; Linden and Bender, 2002]. Some of this is likely related to mosaicism, which may decrease the impact of sex chromosome aneuploidy. Males who are 47/ XXY; 46/XY mosaic may have more functional testicular tissue, which would decrease the severity of hypogonadism. The source of the supernumerary chromosomes (maternal or paternal) or the degree of skewing of X chromosome inactivation may also have an impact, although the evidence for these playing a significant role is mixed [Iitsuka et al., 2001; Zinn et al., 2005; Wikstrom et al., 2006; Zeger et al., 2008].
