22q11.2 microduplication in a family with recurrent fetal congenital heart disease

People carrying a 22q11.2 microduplication display a phenotype varying from normal to severely affected. We report a phenotypically normal female presented with a fetus having a severe congenital heart defect with ventricular septal defect, tricuspid atresia, patent ductus arteriosus and interrupted aortic arch. The pregnant woman had a history of overall three consecutive aberrant pregnancies with tetralogy of Fallot. Standard G-banding karyotype analysis of the parents and the actual pregnancy were normal, while array comparative genomic hybridization (arrayCGH) analysis revealed a 22q11.2 microduplication within the fetus' genome. Fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) tests indicated the affected fetus inherited the interstitial 22q11.2 microduplication from the mother. High-resolution oligonucleotide microarray analysis showed this microduplication is located in the common 3 Mb 22q11.2 deletion region between positions 17.298 Mb and 20.246 Mb with a length of 2.948 Mb. This report demonstrates the remarkable intrafamilial variability of a 22q11.2 microduplication phenotype. The 22q11.2 microduplication carried by one of the healthy parents has most likely contributed to the recurrent fetal heart defects.