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Updating the profile of C-terminal MECP2 deletions in Rett syndrome
  1. A Bebbington1,
  2. A Percy2,
  3. J Christodoulou3,4,
  4. D Ravine5,
  5. G Ho3,
  6. P Jacoby1,
  7. A Anderson1,
  8. M Pineda6,
  9. B Ben Zeev7,
  10. N Bahi-Buisson8,
  11. E Smeets9,10,
  12. H Leonard1
  1. 1Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia
  2. 2Civitan International Research Centre, University of Alabama, Birmingham, Alabama, USA
  3. 3NSW Centre for Rett Syndrome Research, Children's Hospital at Westmead, Sydney, Australia
  4. 4Disciplines of Paediatrics & Child Health and Medical Genetics, University of Sydney, Sydney, Australia
  5. 5West Australian Institute of Medical Research and Centre for Medical Research, University of Western Australia, Perth, Australia
  6. 6Hospital Sant Joan de Deu, Barcelona, Spain
  7. 7Safra Pediatric Hospital, Sheba Medical Center, Ramat-Gan, Israel
  8. 8Université René Descartes—Paris V, Hopital Necker Enfants Malades, Paris, France
  9. 9Centre of Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium
  10. 10Department of Clinical Genetics, Academic Hospital Maastricht, Maastricht, The Netherlands
  1. Correspondence to Dr Helen Leonard, Telethon Institute for Child Health Research, PO Box 855, West Perth 6872, Australia; hleonard{at}


Objectives This study aimed to compare the phenotype of Rett syndrome cases with C-terminal deletions to that of cases with different MECP2 mutations and to examine the phenotypic variation within C-terminal deletions.

Methods Cases were selected from InterRett, an international database and from the population-based Australian Rett Syndrome Database. Cases (n=832) were included if they had a pathogenic MECP2 mutation in which the nature of the amino acid change was known. Three severity scale systems were used, and individual aspects of the phenotype were also compared.

Results Lower severity was associated with C-terminal deletions (n=79) compared to all other MECP2 mutations (e.g. Pineda scale C-terminals mean 15.0 (95% CI 14.0–16.0) vs 16.2 (15.9–16.5). Cases with C-terminal deletions were more likely to have a normal head circumference (odds ratio 3.22, 95% CI 1.53 – 6.79) and weight (odds ratio 2.97, 95% CI 1.25–5.76). Onset of stereotypies tended to be later (median age 2.5 years vs 2 years, p<0.001 from survival analysis), and age of learning to walk tended to be earlier (median age 1.6 years vs 2 years, p=0.002 from survival analysis). Those with C-terminal deletions occurring later in the region had lower average severity scores than those occurring earlier in the region.

Conclusion In terms of overall severity C-terminal deletion cases would appear to be in the middle of the range. In terms of individual aspects of phenotype growth and ability to ambulate appear to be particular strengths. By pooling data internationally this study has achieved the case numbers to provide a phenotypic profile of C-terminal deletions in Rett syndrome.

  • Neurology
  • movement disorders (other than Parkinson)
  • epidemiology

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  • Funding Other Funders: National Institutes of Health and National Health and Medical Research Council.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Princess Margaret Hospital for Children, Perth, Western Australia, Australia.

  • Provenance and peer review Not commissioned; externally peer reviewed.