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Diseases

Genetic and Rare Diseases Information Center (GARD)

MECP2 duplication syndrome


Other Names for this Disease
  • Distal duplication Xq
  • Lubs X-linked mental retardation syndrome (formerly)
  • Mental retardation, X-linked, Lubs type (formerly)
  • MRXSL
  • Telomeric duplication Xq
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

My teenage son has been diagnosed with MECP2 duplication syndrome. What can you tell me about this condition?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is MECP2 duplication syndrome?

MECP2 duplication syndrome is a genetic condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Other signs and symptoms include infantile hypotonia; delayed motor milestones (i.e. sitting up, crawling); recurrent infections; poor or absent speech; seizures; and/or spasticity. MECP2 duplication syndrome occurs when there is an extra copy (duplication) of the MECP2 gene in each cell. This is generally caused by a duplication of genetic material located on the long (q) arm of the X chromosome. The condition is inherited in an X-linked manner. Treatment is based on the signs and symptoms present in each person.[1][2]
Last updated: 7/23/2015

What are the signs and symptoms of MECP2 duplication syndrome?

MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Infants affected by this condition are generally diagnosed with severe hypotonia within the first few weeks of life. This reduced muscle tone can lead to feeding difficulties which may require a feeding tube. Trouble swallowing, gastroesophageal reflux, failure to thrive, and extensive drooling are also common symptoms. Distinctive physical features may be noticed shortly after birth which can include brachycephaly (abnormally flat back of the head), midface hypoplasia (underdevelopment of the middle of the face), large ears, deep-set eyes, prominent chin, and a depressed nasal bridge.[1][2]

Due to hypotonia, affected children often have delayed development of motor milestones such as sitting up and crawling. Approximately, one third of affected people never walk independently and those who are able to walk may have an abnormal gait (style of walking). In most cases, hypotonia gives way to spasticity during childhood. Progressive spasticity, which is generally more pronounced in the legs, may lead to the development of mild contractures. Consequently, many affected adults require the use of a wheelchair.[1][2]

The majority of affected people do not develop the ability to talk. Some may have limited speech during early childhood, but frequently this ability is progressively lost during adolescence.[1]

Other signs and symptoms associated with MECP2 duplication syndrome may include seizures; autistic features; clinically significant constipation and bladder dysfunction.[1][2]

Many people affected by MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections can be life-threatening and as a result, approximately half of affected people succumb by age 25.[1]

In most cases, females with a duplication of the MECP2 gene do not have any symptoms, although depression, anxiety, and autistic features have been described in some. When affected, women with MECP2 duplication syndrome are generally less severely affected than males with the condition.[1]
Last updated: 7/22/2015

What is the long-term outlook for people with MECP2 duplication syndrome?

The long-term outlook (prognosis) for people with MECP2 duplication syndrome varies. Based on the few documented cases in the medical literature, approximately half of affected people succumb before age 25 years. This shortened life expectancy is largely due to immune system dysfunction and an increased risk for recurrent infections.[1]
Last updated: 7/23/2015

How might MECP2 duplication syndrome be treated?

Because MECP2 duplication syndrome affects many different systems of the body, medical management is often provided by a team of doctors and other healthcare professionals. Treatment for this condition varies based on the signs and symptoms present in each person. For example, infants with trouble swallowing and/or other feeding difficulties may require a feeding tube. Early developmental interventions may be recommended to help affected children reach their potential. This may include physical therapy, speech therapy and/or occupational therapy. Medications may be prescribed to treat seizures or spasticity. Recurrent infections are usually treated aggressively with appropriate antibiotics.[1][2]

Please speak with a healthcare provider if you have any questions about your personal medical management plan or that of a family member.
Last updated: 7/23/2015

What causes MECP2 duplication syndrome?

MECP2 duplication syndrome occurs when there is an extra copy (duplication) of the MECP2 gene in each cell. This is generally caused by a duplication of genetic material located on the long (q) arm of the X chromosome. The size of the duplication can vary; however, this does not appear to affect the severity of the condition. People with larger duplications have signs and symptoms that are similar to people with smaller duplications.[3]

The MECP2 gene encodes a protein that is important for normal brain functioning. Although it plays many roles, one of its most important functions is to regulate other genes in the brain by switching them on and off. A duplication of the MECP2 gene leads to the production of excess protein, which is unable to properly regulate the expression of other genes. This results in irregular brain activity, leading to the signs and symptoms of MECP2 duplication syndrome.[3][2]
Last updated: 7/22/2015

Is MECP2 duplication syndrome inherited?

MECP2 duplication syndrome is inherited in an X-linked manner.[3] A condition is considered X-linked if the genetic change 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 the MECP2 gene in each cell is sufficient to cause the condition.

In females (who have two X chromosomes), a duplication of one of the two copies of the gene typically does not cause the disorder. 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 prevents 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 the MECP2 gene, the abnormal chromosome is often preferentially inactivated in many or all cells. This is called "skewed X-inactivation." It prevents some women with an MECP2 duplication from developing features of the duplication since the extra genetic material is not active.

In most cases, MECP2 duplication syndrome is inherited from a mother who has no signs or symptoms of the duplication. Rarely, the condition is not inherited and occurs 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).[3][2]
Last updated: 7/22/2015

References
Other Names for this Disease
  • Distal duplication Xq
  • Lubs X-linked mental retardation syndrome (formerly)
  • Mental retardation, X-linked, Lubs type (formerly)
  • MRXSL
  • Telomeric duplication Xq
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.