TBX2 gene duplication associated with complex heart defect and skeletal malformations.

We report on a patient with mild mental retardation, prenatal onset growth retardation, cerebellar hypoplasia, and complex heart defect including: interventricular septal defect, patent foramen ovale, aortic coarctation, tricuspid valve insufficiency, mitral valve stenosis, and minor skeletal anomalies with hypo-aplasia of the distal phalanges. A SNP-array analysis detected a de novo duplication of 17q23.2, encompassing the TBX2 gene. Animal models argue for a key role of Tbx2 during cardiac and limb development. Accordingly, we hypothesize that the heart malformation and mild digital anomalies found in this patient could be related to TBX2 gene overexpression, suggesting parallel consequences of TBX2 gene dosage imbalances in animals and in humans.