Co-existence of other copy number variations with 22q11.2 deletion or duplication: a modifier for variable phenotypes of the syndrome?

We observed additional copy number variations (CNVs) in 2 of 15 cases with a 22q11.2 deletion or duplication. Both cases were newborn babies referred for severe congenital heart defects. The first case had a deletion with a size of approximately 1.56 Mb involving multiple genes including STS in the Xp22.31 region along with a 22q11.2 deletion. The second case had a duplication of 605 kb in the 15q13.3 region encompassing CHRNA7 and a deletion of 209 kb involving the RBFOX1 gene in the 16p13.2 region, in addition to 22q11.2 duplication.Our observations have shown that additional CNVs are not rare (2/15, 13%) in patients with a 22q11.2 deletion or duplication. We speculate that these CNVs may contribute to phenotype variations of 22q11.2 microdeletion/duplication syndromes as genomic modifiers.It is well known that the phenotype of patients with 22q11.2 microdeletion or microduplication can be extremely variable from near normal to severe developmental disabilities including congenital heart defects, learning disabilities, and risk of psychological problems such as attention-deficit hyperactivity disorder, autism-spectrum disorders and schizophrenia [1,2]. The mechanisms that lead to extreme phenotype variations in this syndrome remain unknown. Prior to the clinical use of microarray based comparative genomic hybridization (array CGH), vast majority of patients with a 22q11.2 deletion or duplication were diagnosed by FISH [3-5], and therefore genomic changes other than the 22q11.2 region were barely known. Here, we report additional genomic aberrations detected by array CGH in two newborns, one had a deletion and the other had a duplication of the 22q11.2 region.The patient was an infant girl, 15 days of age, born to a 23 year old healthy mother. The baby was delivered at the 38th week of gestation by C-section due to nuchal cord. The baby weighted 2.9 kg, with Apgar scores 8 at 1 min, 9 at 5 min, and 9 at 10 min. Management of the infant at delivery included stimulat