Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

MECP2 Duplication Syndrome [F84.9]

OMIM numbers: 300260, 300005 (MECP2)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh, Dr. med. Dagmar Wahl

Scientific Background

The MECP2 duplication syndrome is a X chromosomal recessive disease, caused by a duplication in the chromosomal region Xq28. Affected male patients are mainly characterized by a significant intellectual disability and hypotonia of the trunk and facial muscles. Furthermore, epileptic seizures, progressive spasticity, increased susceptibility to infections as well as mild facial abnormalities, such as large outer ears and a flat nasal bridge, define the clinical phenotype. Other characteristics are a severe developmental disorder with nearly absent speech development. Most patients are not able to walk unaided. Obligate female conductors usually show no clinical signs and symptoms and display a skewed X-inactivation.

The duplicated region Xq28 causing the MECP2 duplication syndrome comprises several genes; the duplication of the MECP2 gene, however, is considered to be the cause for the neurological signs and symptoms. The extent to which the other duplicated genes determine the phenotype has not been clarified yet. In a study of a collective of 134 male patients with intellectual disability as well as severe, usually progressive neurologic signs and symptoms, a duplication in the chromosomal region Xq28 was detected in 2%. According to Lugtenberg et al. 2009, a duplication of the MECP2 gene should be taken into consideration in male patients with neurodegenerative diseases and intellectual disability of unknown cause.