Heritable Thoracic Aortic Diseases (HTAD) is increasingly attentive diagnosis. The incidence of dissections in the thoracic aorta generally has been estimated to 6/100 000 inhabitants per year, and 20 to 40 % of them have been estimated to be familial.
In most carriers, aortic dissection is proceeded by slowly growing aortic aneurysms, usually in the ascending aorta. Eventually, an intimal tear will initiate an aortic dissection and at that time, the diameter of the aneurysm usually is substantially increased. A few hereditary syndromes like Marfans-, Loeys-Dietz- and Ehlers-Danlos - of the vascular type are associated with high risk of aortic dissections. During the last few years, additional genes have been possible to couple to familial aortic diseases. However, in three out of four families, genetic analyses are still negative. Finding disease-causing genes is very important, simplifying screening in the family, as the phenotype is usually vague in young adult age. In addition, the phenotype, prognosis and preventive measures have been found to be different for the different diseases.
In our families with Heritable Thoracic Aortic Diseases (HTAD) we aim to search for previously unknown genes causing the disease. For this, we perform whole genome sequencing in individuals from large families with HTAD. We also try to closely relate genotype to phenotype as phenotypes are well characterized in our families with HTAD; Age at dissections, distribution of aneurysms, aortic size at dissection, other symptoms etc.
In clinical practice, the genetic cause is still unknown in most families why it is of great importance to define the phenotype.
In our first examined subjects, (n=130) we found that phenotypic screening of aortic diameters MRI and echocardiography in families with HTAD, does not detect all carriers, and thus have to be repeated. This is in contrast with guidelines, which have not recommended repeated screening.
In addition, in this cohort, we show that echocardiography and MRI show almost identical aortic diameters. Thus, in families with aortic disease confirmed to the ascending aorta, echocardiography could replace many investigations with MRI.
In one of our largest families, we found a disease causing mutation in the MYLK-gene. There is only one previous publication of families with MYLK-mutations as a cause of aortic dissections. Together with an international group, we found that all available data show that aortic diameters are of low value as predictors of dissections in these patients. Therefore, the recommendation now is to recommend MYLK-HTAD patients prophylactic surgery at a certain age as in some hereditary cancers.