Clinical and Genetic Studies in Inherited Cardiovascular Malformations

Cardiovascular malformations comprise a broad spectrum of anomalies of the heart and blood vessels, including congenital heart malformations (CHM) and aortic aneurysms, the two main topics of this thesis. These conditions lead to significant morbidity and mortality both in infancy and adulthood. A substantial proportion of cardiovascular malformations have a genetic background, including large chromosomal abnormalities, submicroscopic chromosome deletions or duplications, and single gene mutations. However, the majority of cardiovascular malformations is thought to be due to multifactorial inheritance, involving a multitude of mutations in susceptibility genes superposed on unfavorable environmental and life style factors. In the past decade, great progress has been made in the unravelling of genes involved in cardiovascular malformations. This made it possible to understand the genetic pathways and underlying pathophysiologic mechanisms, and develop therapeutic and preventive measures. It also led to the need for multidisciplinary cardiogenetic clinics in order to improve diagnosis and treatment of cardiovascular diseases. Such a multidisciplinary cardiogenetic clinic has been established in the (Paediatric) Cardiology Department of the Erasmus Medical Center in Rotterdam. In this setting most patients described in this thesis were studied. With the enthusiastic participation of these patients, their families and physicians, scientific studies were initiated to understand the genetic cause of cardiovascular malformations.

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