Kate Gardiner and David Chitayat contributed equally to this work.
Article first published online: 14 MAY 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 6, pages 1388–1394, June 2012
How to Cite
Gardiner, K., Chitayat, D., Choufani, S., Shuman, C., Blaser, S., Terespolsky, D., Farrell, S., Reiss, R., Wodak, S., Pu, S., Ray, P. N., Baskin, B. and Weksberg, R. (2012), Brain abnormalities in patients with Beckwith–Wiedemann syndrome. Am. J. Med. Genet., 158A: 1388–1394. doi: 10.1002/ajmg.a.35358
How to Cite this Article: Gardiner K, Chitayat D, Choufani S, Shuman C, Blaser S, Terespolsky D, Farrell S, Reiss R, Wodak S, Pu S, Ray PN, Baskin B, Weksberg R. 2012. Brain abnormalities in patients with Beckwith–Wiedemann syndrome. Am J Med Genet Part A. 158A:1388–1394.
- Issue published online: 17 MAY 2012
- Article first published online: 14 MAY 2012
- Manuscript Accepted: 5 FEB 2012
- Manuscript Received: 22 AUG 2011
- Beckwith–Wiedemann syndrome;
- Dandy–Walker malformation;
- posterior fossa;
- chromosome 11p15.5;
- tumor predisposition;
- genomic imprinting
Beckwith–Wiedemann syndrome (BWS) is an overgrowth disorder with variability in clinical manifestations and molecular causes. In most cases, patients with BWS have normal development. Cases with developmental delay are usually attributed to neonatal hypoglycemia or chromosome abnormalities involving copy number variation for genes beyond the critical BWS region at 11p15.5. Brain abnormalities have not previously been recognized within the BWS phenotypic spectrum. We report on seven cases of BWS associated with posterior fossa abnormalities. Of these, two cases presented with Blake's pouch cyst, two with Dandy–Walker variant (DWV; hypoplasia of the inferior part of the vermis), one with Dandy–Walker malformation (DWM) and one with a complex of DWM, dysgenesis of the corpus callosum and brain stem abnormality. In all these cases, molecular findings involved the centromeric imprinted domain on chromosome locus 11p15.5, which includes imprinting center 2 (IC2) and the imprinted growth suppressor gene, CDKN1C. Three cases had loss of methylation at IC2, two had CDKN1C mutations, and one had loss of methylation at IC2 and a microdeletion. In one case no mutation/methylation abnormality was detected. These findings together with previously reported correlations suggest that genes in imprinted domain 2 at 11p15.5 are involved in normal midline development of several organs including the brain. Our data suggest that brain malformations may present as a finding within the BWS phenotype when the molecular etiology involves imprinted domain 2. Brain imaging may be useful in identifying such malformations in individuals with BWS and neurodevelopmental issues. © 2012 Wiley Periodicals, Inc.