MECP2 DUPLICATION SYNDROME

MECP2 duplication syndrome is an X-linked recessive disorder caused by a duplication in the Xq28 chromosomal region. Duplication of the MECP2 gene in this region is considered to be the cause of the neurological symptoms. It has been found that the size of the duplication correlates with the severity of the phenotype. In male patients with neurodegenerative disease and mental retardation of unknown cause, testing for duplication of the MECP2 gene should be considered.

Symptoms

Affected male patients are mainly characterized by significant intellectual disability 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 ears and a flat nasal root define the clinical phenotype. There is a severe developmental disorder with largely absent speech development. Independent walking is often not achieved. Obligate carriers usually show no clinical symptoms and exhibit skewed X inactivation.

Causes

The duplicated Xq28 region responsible for MECP2 duplication syndrome comprises several genes, with duplication of the MECP2 gene 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 established. 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%. Therefore, testing for a duplication of the MECP2 gene should be considered in male patients with neurodegenerative disease and mental retardation of unknown cause.

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