Syndromes associated with more than one additional X chromosome are much less common, and thus have not been present in enough numbers in any of the published prospective studies to provide a description of the phenotype free of potential referral bias. The cases that have been reported are generally associated with more severe developmental delays and physical manifestations, most frequently affecting the skeletal, cardiac, and genital systems. Although individuals with two additional X chromosomes are typically taller than normal, this begins to reverse with three additional chromosomes, such that females with pentasomy X (49,XXXXX) and 49,XXXXY males are often below average height [Linden et al., 1995; Visootsak et al., 2007].
