Study of the genetic causes of disorders of the aorta, arteries and cardiac valves

Within the thoracic aortic aneurysms and dissection, two main groups can be
distinguished: syndromic and non-syndromic forms. Within the syndromic group,
such as Marfan syndrome, Ehlers-Danlos syndrome and Loeys-Dietz syndrome, very
often other connective tissue symptoms and signs (affecting eyes, skin, joints,
internal organs,*) are present. For this syndromic group, the genetic basis of
most disorders is known but very little is know about the genetic factors that
modify the phenotypical severity. With in the non-syndromic group about 20% of
the patients have a positive family history indicating a strong genetic
predisposition. Some of the genes underlying non-syndromic thoracic aortic
aneurysm and dissection have been identified but for the majority the genetic
cause is unknown. An important group within the non-syndromic forms, are the
thoracic aneurysms associated with bicuspid aortic valve. Bicuspid aortic
valves are the most common congenital heart defect in humans with a prevalence
of 1-2% of the population. The genetic basis van bicuspid related thoracic
aortic aneurysm is unknown.

To gain a better insight into the genetic factors that play a role in the
etiology of the thoracic aortic aneurysm with the following specific aims:
1. Study of specific geneitc factos that play a role in the pathogenesis of
both syndromic and non-syndromic aortic aneurysms.
2. Identify the role of modifiers of the phenotypical variation in genetic
forms of aortic aneurysm, eg Marfan syndrome.
3. Unravel the genetic basis van bicuspid aortic valve related aneurysms.

Gathering and genetic analysis of DNA from blood sampling of patients with
thoracic aortic aneurysm and/or valve defects. In rare case, investigations
will also happen via skin biopsies (fibroblast culture) or via restmaterial
obtained from cardiovascular surgery (heart valve, aortic wall)

Blood test: causes a short pain when the needle penetrates the skin. Prolonged
bleeding can occur at the place of punction. A blue discoloration of the skin
can appear. This disappears within a fortnight. There is a limited risk of
fainting or infection.
Skin biopsy: A biopsy of the skin of maximum 5mm is taken from a non-visible
place (mostly at the inner upper arm). This is done under local anaesthesia.
The skin defect will be stitched or sometimes closed with Steristrips. The
injection of the local anaesthetic can briefly cause pain. There is a small
risk of bleeding or infection afterwards. The wound normally heals within a
fortnight. Occasionally, a small round scar remains visible.
Aortic/valve biopsy: For these procedures only material that normally would be
destroyed will be used.