MECP2 Duplication Syndrome

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by early-onset hypotonia, feeding difficulty, gastrointestinal manifestations including gastroesophageal reflux and constipation, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected individuals), and seizures (in ~50%). MECP2 duplication syndrome is 100% penetrant in males. Occasionally females have been described with a MECP2 duplication and a range of findings from mild intellectual disability to a phenotype similar to that seen in males. In addition to the core features, autistic behaviors, nonspecific neuroradiologic findings on brain MRI, mottled skin, and urogenital anomalies have been observed in several affected boys.

Diagnosis/testing: The diagnosis of MECP2 duplication syndrome is established in an individual by identification of a heterozygous whole-gene duplication of MECP2 on molecular genetic testing.

Management: Treatment of manifestations: Routine management of feeding difficulties, constipation, developmental and speech delays, spasticity, and seizures. Physical therapy to maintain range of motion to reduce likelihood of contractures. Prompt antibiotic treatment for respiratory infections; all vaccines should be given; consider gastrostomy tube if aspiration is present. Social work and care coordination as indicated.

Surveillance: Routine monitoring for growth, feeding issues, constipation, reflux, loss of speech, progressive spasticity, seizure disorder and response to anti-seizure medication, infections, and autistic-like features.

Genetic counseling: MECP2 duplication syndrome is inherited in an X-linked manner. The majority of affected males have inherited the MECP2 duplication from a heterozygous mother; however, de novo genetic alterations have been reported. If the mother of the proband has a MECP2 duplication, the chance of transmitting it in each pregnancy is 50%. Males who inherit the MECP2 duplication will be affected; females who inherit the MECP2 duplication are typically asymptomatic but may exhibit clinical manifestations ranging from mild nonspecific intellectual disability to a severe phenotype similar to that observed in males. If the mother of the proband has a balanced structural chromosome rearrangement involving the Xq28 region, the risk to sibs depends on the specific chromosome rearrangement. Once the MECP2 duplication has been identified in an affected family member (and/or the mother of the proband is found to be a carrier of a balanced translocation), prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.

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