MECP2-Related Disorders and Epilepsy Phenotypes

Abstract

AbstractMECP2 (methyl-CpG binding protein-2) gene, located on chromosome Xq28, encodes for a protein particularly abundant in the brain that is required for maturation of astrocytes and neurons and is developmentally regulated. A defective homeostasis of MECP2 expression, either by haploinsufficiency or overexpression, leads to a neurodevelopmental phenotype. As MECP2 is located on chromosome X, the clinical presentation varies in males and females ranging from mild learning disabilities to severe encephalopathies and early death. Typical Rett syndrome (RTT), the most frequent phenotype associated with MECP2 mutations, primarily affects girls and it was previously thought to be lethal in males; however, MECP2 duplication syndrome, resulting from a duplication of the Xq28 region including MECP2, leads to a severe neurodevelopmental disorder in males. RTT and MECP2 duplication syndrome share overlapping clinical phenotypes including intellectual disabilities, motor deficits, hypotonia, progressive spasticity, and epilepsy. In this manuscript we reviewed literature on epilepsy related to MECP2 disorders, focusing on clinical presentation, genotype–phenotype correlation, and treatment.