Phenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants

Genomic rearrangements are an important source of genetic and phenotypic variation. Rare, recurrent copy-number variants of pathogenic significance, termed genomic disorders, were originally identified in persons with a characteristic set of clinically recognizable features, such as the Smith?Magenis syndrome, the Sotos syndrome, and the Williams?Beuren syndrome. Although unexplained phenotypic variation and differences in severity have long been recognized among patients with the same genomic disorder,1?5 comparatively recent discoveries of potentially pathogenic copy-number variants have broadened the phenotypic range associated with a given variant to include entirely distinct diseases. High-throughput analyses of patient populations have implicated the same copy-number variants . . .