MECP2 DUPLICATION SYNDROME

MECP2 duplication syndrome is an X-linked recessive disorder caused by a duplication in the chromosomal region Xq28. The affected male patients are mainly characterized by marked mental retardation and hypotonia of the trunk and facial muscles. Furthermore, epileptic seizures, progressive spasticity, an increased susceptibility to infections and slight facial abnormalities such as large auricles and a flat nasal root define the clinical phenotype. There is a severe developmental disorder with largely absent speech development. Walking freely is often not possible. Obligate carriers usually show no clinical symptoms and exhibit displaced X-inactivation.

The duplicated Xq28 region causative for MECP2 duplication syndrome comprises several genes, whereby the duplication of the MECP2 gene is considered to be the cause of the neurological symptoms. The extent to which the additionally duplicated genes have an influence on the phenotype has not yet been clearly clarified. However, a study by Peters et al. 2019 showed that the size of the duplication correlates with the severity of the phenotype. In a study of 134 male patients with mental retardation and severe, mostly progressive neurological symptoms, a duplication in the chromosomal region Xq28 was detected in 2%.

References

Peters et al. 2019, Clin Genet 95:575 / Lim et al 2017, Clin Genet 91:557 / El Chehadeh et al. 2017, Clin Genet 91:576 / Reardon et al. 2010, Eur J Pediatr 169:941 / Lugtenberg et al. 2009, Eur J Hum Genet 17:444 / Clayton-Smith et al. 2009, Eur J Hum Genet 17:434 / Kirk et al. 2009, Clin Genet 75:301 / Friez et al. 2006, Pediatrics 118:e1687 / Van Esch et al. 2005, Am J Hum Genet 77:442