Conversely, MECP2 duplication syndrome is associated with the X-linked recessive trait and skewed XCI in female carriers, which suggests that overexpression of neighboring genes in the duplicated region, rather than MECP2 itself, may induce negative selection in the early embryo, leading to a preferential XCI.28 Alternatively, embryonic damage may be more severe in cases of MECP2 duplication compared with MECP2 nucleotide changes, although this remains controversial. Here, MECP2 is linked to Down syndrome.