Co-occurrence of 4p16.3 deletions with both paternal and maternal duplications of 11p15: modification of the Wolf-Hirschhorn syndrome phenotype by genetic alterations predicted to result in either a Beckwith-Wiedemann or Russell-Silver phenotype.

Paternal duplications of chromosome region 11p15 can result in Beckwith-Weidemann syndrome (BWS), whereas maternal duplications of the same region on 11p15 can result in Russell-Silver syndrome (RSS). These two syndromes have numerous opposing phenotypes, especially with regards to growth parameters. The differences in the phenotype are proposed to be due to altered dosage of imprinted genes that control growth within this region of 11p15. Wolf-Hirschhorn syndrome (WHS) is due to deletions of a region in 4p16.3 and there is no known parent-of-origin effect for deletions of the WHS critical region, and no genes are known to be imprinted in this region. We report on three individuals with very similar unbalanced translocations resulting in a derivative chromosome 4 with both a deletion of 4p16.3 and a duplication of 11p15. Two of these individuals are family members with one inheriting the derivative 4 from her balanced mother and the other inheriting the derivative 4 from his balanced father. The third individual is unrelated and inherited his derivative 4 from his balanced father. While the findings of these individuals included some features of WHS and RSS or BWS, the phenotypes as an aggregate are distinct from these syndromes. The genomic and phenotypic characterization of these three individuals demonstrates how unbalanced translocations can result in the modification of chromosome duplication and deletion syndromes and identifies genomic architecture that may be responsible for mediating a recurrent translocation between 4p and 11p.