Genetic

The genesis of congenital heart defects (CHD) has multifactorial causes. Up to now those affected and their families can be counselled only in terms of the empirical risk of recurrence. There is evidence, however, for a significant genetic component of CHDs, as the recurrence risk in the children of an affected parent is eight times as high as in the general population. In order to systematically examine the genetic causes of the most frequent congenital cardiac malformations, patients with familial occurrence of CHDs need to be studied. The National Registry for Congenital Heart Defects (registered association) provides a unique opportunity to find such patients and study them in sufficient numbers.

Changes in specific genes that control the cardiovascular development can lead to the emergence of congenital heart defects (CHD) between the third and seventh week of gestation. During the last few years, several molecular mechanisms that play a role in the morphologic and functional development of the heart have been elucidated by using model organisms. Besides larger chromosomal aberrations, point mutations were identified in single genes that follow a monogenic inheritance. However, in patients with congenital heart defects the inheritance pattern is rarely monogenic, but mostly complex. Little is as yet known about the genetic factors that play a role in the etiology of this multifactorial disease.

This study aims to identify disease-causing genes in CHD. For this purpose, molecular genetic examinations (mutation analyses of selected candidate genes, genome-wide linkage studies) are performed in familial cases of CHDs.

The study population is made up of patients who have at least one other affected relative with a congenital heart defect registered with the National Registry for Congenital Heart Defects.

By using the genetic data acquired, the study aims at contributing to an improved assessment of the causes and the recurrence risk of a CHD, so that those affected can be offered better means of prevention, diagnosis and treatment in the long term.