Chromosome Xq duplication

The signs and symptoms of a chromosome Xq duplication vary significantly depending on the size of the duplication, the sex of the affected person, and the genes found on the duplicated segment of the chromosome. In general, males with a chromosome Xq duplication are generally more severely affected than females with the duplication. Common features that may be shared by males with this duplication include:^[1]

• 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.^[2][3]

People with a chromosome Xq duplication have an extra copy of the genetic material located on the long arm (q) of the X chromosome in each cell. The amount of extra genetic material and which genes are duplicated varies in each person depending on the size and location of the duplication.

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.^[1][4]

Chromosome Xq duplication is inherited in an X-linked manner. A condition is considered X-linked if the mutated gene that causes the condition is located on the X chromosome, one of the two sex chromosomes (the Y chromosome is the other sex chromosome). In males (who have only one X chromosome), a duplication of Xq in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a duplication of Xq typically does not cause any signs or symptoms.

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.^[4][5]

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.^[2] When this happens, it is called a de novo duplication (occurring as a new genetic change for the first time in the affected person).

There are several different specialized tests that can be used to diagnose a chromosome Xq duplication. These include:^[4]

• Karyotype - a karyotype is a laboratory test that produces an image of a person's chromosomes. This test can be used to diagnose large duplications.
• FISH - a laboratory technique that is used to detect and locate a specific DNA sequence on a chromosome. During FISH, a chromosome is exposed to a small DNA sequence called a probe that has a fluorescent molecule attached to it. The probe sequence binds to its corresponding sequence on the chromosome. This test can be used in combination with karyotyping for duplications that are too small to be seen on karyotype, alone. However, FISH is only useful if the person ordering the test suspects there is a duplication of a specific region of Xq since a diagnosis can only be made if the probe binds the duplicated sequence.
• Array CGH - a technology that detects duplications that are too small to be seen on karyotype.

Because chromosome Xq duplication affects many different systems of the body, medical management is often provided by a team of doctors and other healthcare professionals. Treatment for this duplication varies based on the signs and symptoms present in each person. For example, parenteral nutrition and/or other dietary interventions may be recommended for infants and young children with feeding difficulties to prevent poor growth and malnutrition. Children with a speech and/or language delay or other problems with communication may be referred for speech and communication therapy. Medications may be prescribed to treat seizures. Children with delayed motor milestones (i.e. walking) may be referred for physical or occupational therapy. Prophylactic antibiotics may be considered in people with frequent infections.^[4]

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.^[2][1]