European Journal of Pediatrics

, Volume 169, Issue 8, pp 941–949 | Cite as

Progressive cerebellar degenerative changes in the severe mental retardation syndrome caused by duplication of MECP2 and adjacent loci on Xq28

  • William Reardon
  • Veronica Donoghue
  • Anne-Marie Murphy
  • Mary D. King
  • Philip D. Mayne
  • Nina Horn
  • Lisbeth Birk Møller
Original Paper

Abstract

Localised duplications, involving the MECP2 locus, at Xq28 have been associated with a syndrome comprising X-linked mental retardation, hypotonia and recurrent infections in males. We now present neuroradiological evidence that progressive cerebellar degenerative changes may also be a consistent feature of this syndrome, emerging in the second decade of life. We report seven affected males, from three different families who, in addition to the previously described clinical findings, have a reduction in the volume of the white matter and mild dilatation of the lateral ventricles. Three of the older patients show a consistent cerebellar degenerative phenotype. Furthermore, we describe the first female affected with the disorder. The female was mildly affected and shows X-inactivation in the ratio of 70:30, demonstrating that X-inactivation cannot be exclusively relied upon to spare the female carriers from symptoms. In conclusion, there is a radiological phenotype associated with Xq28 duplication which clearly demonstrates progressive degenerative cerebellar disease as part of the syndrome.

Keywords

Xq28 duplication MECP2 Cerebellar atrophy X-linked mental retardation 

Abbreviations

MLPA

Multiple ligation-dependent probe amplification

Array CGH

Array comparative genome hybridisation

Kb

Kilobases

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • William Reardon
    • 1
    • 4
  • Veronica Donoghue
    • 2
  • Anne-Marie Murphy
    • 2
  • Mary D. King
    • 2
  • Philip D. Mayne
    • 2
  • Nina Horn
    • 3
  • Lisbeth Birk Møller
    • 3
  1. 1.Regional HospitalLimerickIreland
  2. 2.Children’s University HospitalDublin 1Ireland
  3. 3.Kennedy CenterGlostrupDenmark
  4. 4.National Centre for Medical GeneticsOur Lady’s Hospital for Sick ChildrenDublin 12Ireland

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