DISSECTION OF GENETIC MECHANISMS OF LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION DEFECTS BY HIGH-RESOLUTION ARRAY-CGH

Congenital cardiac abnormalities are the most frequent defects of the embryo development and are detected with a frequency of 4-8/1000 newborns. Many of these defects demand a surgical correction that can result either in a complete recovery or in a heart disease that will accompany the individual for all life. In few particular situations the treatment can be simply therapeutic. As obvious, a baby with a cardiac defect gives rise remarkable anxieties in the relatives initially limited to the vital abilities to the same baby and to his/her quality of life after proper treatments and, subsequently, to the risk that the successive pregnancies result newly in the birth of an affected child. Currently, the genetic bases of congenital cardiac defects are little known but it is clear that the mutations for some genes cause isolated cardiac defects. Moreover, the enormous improvement of the resolution abilities to the echography is anticipating the detection of the cardiac defects from birth to the prenatal life when these defects are ten times more frequent. At the moment parents have to choose between the risk to abort a fetus that, after proper cardiac correction, might have a normal life or to keep a fetus that might be affected by cardiac failure for all his/her life or might even be at risk of death in the first years of life. We intend to study the genetic mechanisms of left ventricular outflow tract obstruction that in its more severe form, hypoplastic left heart syndrome, is the most frequent cause of death due to heart defects in the first week of life. The extension of genetic and clinical investigations to parents and relatives will allow us to understand the genetics of the variable expression of this defect and ultimately to establish a precise recurrence risk.