17. Chromosome 2p duplication associated mechanisms and clinical presentations

Abstract

Chromosome 2p duplication, also known as trisomy 2p, is a rare chromosome abnormality, which is associated with developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most of the reported cases involving trisomy 2p include additional copy number variants in other regions of the genome and are usually small in size. Little is known about the clinical outcomes of large duplications of chromosome 2p alone. In this study, we analyzed 8 patients with large chromosome 2p duplications ranging in size from 9.3 Mb to 89 Mb. These duplications were identified in association with inverted duplication, tandem duplication, and duplication as the result of translocation, with no other copy number variant identified by microarray analysis. Seven out of 8 patients had confirmation by conventional cytogenetics and all of the translocations were confirmed by FISH. Interestingly, one case is a patient with mosaic complete trisomy 2p, who has a de novo (X;2) chromosomal translocation. X-inactivation was shown for the derivative X chromosome, yet it does not appear to extend into the chromosome 2 material. While patients share common clinical manifestations including developmental delay, hemifacial hypoplasia, cleft palate, and short stature, they also have distinct features such as hypotonia, cerebellar agenesis/hypogenesis, and corpus callosum agenesis, which might result from a gene dosage effect of the duplication. Triplosensitivity has been reported in patients with duplications covering 2p24.3 region. Global developmental delay and autism have also been reported in patients with de novo microduplications of 2p15p16.1. In conclusion, large chromosome 2p duplications could result from inverted or tandem duplications within chromosome 2, or translocations involving chromosome 2 and other chromosomes. Partial or complete trisomy 2p are commonly associated with developmental delay, and additional clinical features may be related to gene dosage effect.