Chromosome Xq duplication is a chromosome abnormality that affects many different parts of the body. People with this condition have an extra copy of the genetic material located on the long arm (q) of the X chromosome in each cell. The severity of the condition and the associated signs and symptoms vary based on the size and location of the duplication; the genes involved; and the sex of the affected person. In general, males are typically more severely affected than females and often experience intellectual disability, developmental delay, short stature, abnormalities of the reproductive organs, and distinctive craniofacial features. Many females with this duplication do not have any symptoms or are only affected with short stature; however, some may be just as severely affected as males with the condition. Most cases are inherited in an X-linked manner, often from a mother with no signs or symptoms of the condition. Treatment is based on the signs and symptoms present in each person.

• Hypotonia
• Feeding issues as an infant
• Brain abnormalities
• Failure to thrive
• Developmental delay
• Intellectual disability
• Speech/language delay and other difficulties with communication
• Frequent infections
• Short stature
• Microcephaly (unusually small head)
• Craniofacial abnormalities
• Abnormal development of reproductive organs
• Dysfunction of the endocrine system
• Seizures

Many females with this duplication do not have any symptoms or are only affected with short stature. However, some may be just as severely affected as males with the condition.

Scientists suspect that the features seen in people affected by this condition are caused by the duplication and/or disruption of certain genes found on Xq. The consequences of over-expression of many of the genes located in this region are not well understood. However, there are three specific genes that are fairly well characterized. The duplication of a particular gene, MECP2, may be responsible for many of the signs and symptoms found in affected people. An extra copy of the MECP2 gene is often associated with moderate to severe intellectual disability, developmental delay, weak muscle tone in infancy, feeding difficulties, and/or frequent respiratory infections. An extra copy of the PLP1 gene can be associated with brain abnormalities that are often seen in a group of genetic disorders called leukodystrophies (rare diseases that affect the cells of the brain). Duplication of the OPHN1 gene has been reported in people with severe intellectual disability, microcephaly, and usual facial features. Researchers are working to learn more about the other genes on Xq that may contribute to the features seen in people with a chromosome Xq duplication.

In many cases, the chromosome Xq duplication is inherited from a mother who has no signs or symptoms of the duplication. The X chromosome is one of the two sex chromosomes (the Y chromosome is the other sex chromosome). Males have an X chromosome and a Y chromosome, while females have two X chromosomes. Early in the development of females, one of the two X chromosomes is randomly and permanently inactivated in each cell (called X-inactivation). X-inactivation prevent female cells from having twice as many functional X chromosomes as males. Because X-inactivation is usually random, the X chromosome inherited from the mother is active in some cells, and the X chromosome inherited from the father is active in other cells. However, when a female has an X chromosome with a duplicated copy of Xq, the abnormal chromosome is often preferentially inactivated in many or all cells. This is called "skewed X-inactivation." It prevents some women with a chromosome Xq duplication from developing features of the duplication since the extra genetic material is not active.

Some cases of chromosome Xq duplication are not inherited and occur due to a random event during the formation of the egg or sperm, or in early fetal development. When this happens, it is called a de novo duplication (occurring as a new genetic change for the first time in the affected person).

Please speak to your healthcare provider if you have any questions about your personal medical management plan.

The long-term outlook (prognosis) for people with chromosome Xq duplication varies depending on the signs and symptoms present in each person and the severity of the condition. In general, males are typically more severely affected than females. Many females do not have any signs or symptoms of the duplication or are only affected with short stature. However, some may be just as severely affected as males with the condition.