Clinical and submicroscopic findings of two prenatal cases with inv dup del(8p) syndrome

Chromosome 8p inverted duplication deletion syndrome [inv dup del(8p)] is a rare disease characterized by intellectual disability, congenital heart defects, central nervous system abnormalities, and dysmorphic features. To date, the chromosomal alterations have been presented at the molecular level in only a small number of prenatal cases. Here, we report two prenatal cases, one with increased nuchal translucency, cerebellar vermis agenesis, a solitary interhemispheric cyst, and ventricular septal defect (VSD) and the other with VSD and discordance between right and left heart ventricles. Conventional cytogenetic, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (array CGH) analyses revealed that both cases had inv dup del(8p). This presented as a deletion larger than 6.5 megabases (Mb) distal to the 8p23 (8p23.1-pter) region, followed by an intermediate intact segment, and then an inverted duplicated proximal segment of approximately 30 MB, from 8p23.1 to 8p11.1 in the first fetus and from 8p23.1 to 8p11.21 in the second. The GATA4 gene has now been implicated in the cardiac defects associated with deletions of 8p23.1. Although both fetuses had VSD, GATA4 was located in the intact region, whereas the NRG1 gene, which is necessary for heart development, was duplicated in our cases. We suggest that duplication of the NRG1 gene could be responsible for the cardiac findings in our cases, but further studies are necessary to confirm this hypothesis.