About 1/1000 apparently normal females has a 47,XXX (trisomy X) karyotype. Physical anomalies are rare. Menstrual irregularity and infertility sometimes occur. Affected girls may have mildly impaired intellect and may have more school problems than siblings. Advanced maternal age increases risk of trisomy X, and the extra X chromosome is usually maternally derived.
Although rare, 48,XXXX and 49,XXXXX females exist. There is no consistent phenotype. The risk of intellectual disability and congenital anomalies increases markedly when there are > 3 X chromosomes. The genetic imbalance in early embryonic life may cause anomalous development.
(See also Overview of Chromosomal Anomalies and see Overview of Sex Chromosome Anomalies.)
