Molecular genetics of familial heart disease

It is becoming increasingly clear that genetic defects are involved in a
significant number of cardiac disorders, such as rhythm disturbances,
cardiomyopathies and a subset of congenital heart diseases (CHD). Through
identification of genes that are involved in these disorders, insight in the
pathophysiology of the disorders and the functions of the mutated genes was
gained, and the effects of early treatment on the prognosis of the disorder
could be evaluated. However, in the majority of families with multiple affected
individuals with CHD or aortic aneurysm no mutation is identified in any of the
genes that are currently known to be involved. This implies genetic
heterogeneity of these disorders.
In this study we aim to identify genetic causes for several familial cardiac
disorders, i.e. (different types of) CHD and aortic aneurysms. This will
provide insight in the aetiology and heredity of these diseases. This knowledge
can contribute to improved medical care for patients and their relatives, in
terms of counselling, screening and treatment.

The aim of this study is to identify genetic defects underlying CHD and aortic
aneurysms. This will provide insight in the aetiology and heredity of these
diseases.

Families with two or more affected patients with CHD and/or an aortic aneurysm
will be approached for participation. Participants will undergo the following
investigations: medical history taking, ECG, echocardiogram and cardiac MRI
(when indicated). Furthermore, blood will be drawn (20 ml), from which DNA will
be isolated (in very young children a mouth-swab or saliva kit can be used
instead). In each individual family it will be determined which DNA analysis
technique is feasible for identification of involved genes. Techniques that may
be used are linkage analysis, Sanger-sequencing, exome sequencing, whole genome
sequencing, array CGH and RNA-sequencing.

No significant risks areassociated with participation in this study.
However, there is a possibilty that results will be generated that may be of
clinical relevance to the partcipant or his/her relatives. This may involve
genetic results related to cardiac disease, as well as coincidental findings
not related to the cardiac disorder though clinically relevant. In case of such
finding, we will inform the participant in general terms about the finding and
its clinical relevance. He or she can decide if he wants to be informed more
extensively and to seek treatment. If necessary, participants will be counseled
about this finding at de clinical genetics outpatient clinic. If a partcipant
does not want to be informed in global terms about such findings, he or she
cannot participate in the study.