Progressive cerebellar degenerative changes in the severe mental retardation syndrome caused by duplication of MECP2 and adjacent loci on Xq28.
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.
Reardon
William
W
Regional Hospital, Dooradoyle, Limerick, Ireland. willie.reardon@olhsc.ie
Donoghue
Veronica
V
Murphy
Anne-Marie
AM
King
Mary D
MD
Mayne
Philip D
PD
Horn
Nina
N
Birk Møller
Lisbeth
L
D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D018450:Disease Progression; D005190:Family; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D020547:Lateral Ventricles / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D038901:X-Linked Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012737:Sex Factors; D014057:Tomography, X-Ray Computed; D049951:X Chromosome Inactivation
D051783:Methyl-CpG-Binding Protein 2