Aspects of speech-language abilities are influenced by MECP2 mutation type in girls with Rett syndrome

Am J Med Genet A. 2015 Feb;167A(2):354-62. doi: 10.1002/ajmg.a.36871. Epub 2014 Nov 26.


This study investigates relationships between methyl-CpG-binding protein 2 gene (MECP2) mutation type and speech-language abilities in girls with Rett syndrome. Cross-sectional data on 766 girls, aged 15 years and under, with genetically confirmed Rett syndrome was obtained from the Australian Rett Syndrome Database (ARSD) (n = 244) and the International Rett Syndrome Phenotype Database (InterRett) (n = 522). Relationships between MECP2 mutation type and age of regression in speech-language abilities, and the level of speech-language abilities before and after this regression were investigated. The females had a median age of 4.95 years in the ARSD and 5.25 years in InterRett. The majority (89%, 685/766) acquired speech-language abilities in the form of babble or words at some point in time. Of those who acquired babble or words, 85% (581/685) experienced a regression in these abilities. Those with a p.Arg133Cys mutation were the most likely to use one or more words, prior to (RRR = 3.45; 95% CI 1.15-10.41) and after (RRR = 5.99; 95% CI 2.00-17.92), speech-language regression. Girls with Rett syndrome vary in their use of speech and language, and in their experience of speech-language regression and these variations are partly explained by genotype.

Keywords: MECP2; Rett syndrome; genotype-phenotype correlation; language; regression; speech.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Australia / epidemiology
  • Child
  • Child, Preschool
  • Databases, Factual
  • Female
  • Genetic Association Studies
  • Humans
  • Infant
  • Language*
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Mutation*
  • Rett Syndrome / diagnosis*
  • Rett Syndrome / epidemiology
  • Rett Syndrome / genetics*
  • Speech*


  • Methyl-CpG-Binding Protein 2