Why are some children born with cardiac malformations?

Why are there families with several cases of cardiac malformations? Over the last decade, our knowledge of molecular cascades regulating cardiac development and tools for genetic dissection of human disease traits have rapidly expanded. We have now put together a large cohort of multiplex families, i.e. with several affected members, with an emphasis on left ventricular outflow tract obstructions (200+ families, 1500+ probands enrolled). We are using SNP genotyping for linkage and association analysis, as well as the identification of copy number variants which may be causative for the diseases we study. Our goal is to identify novel chromosomal regions and genes causing congenital heart disease. We have recently identified a novel syndrome of aortic stenosis, septal defects and atrial fibrillation on chromosome Xq28. Ultimately, our goal is to establish genotype-phenotype correlations, in order to develop better diagnostic strategies and therapeutic stratification for patients with congenital heart disease.