Objectives: Hereditary diseases of the thoracic aorta carry a high risk of aortic aneurysm or even acute aortic dissection or rupture. Making the right diagnosis is essential for optimal medical therapy and proper monitoring of the disease as well as to identify at-risk individuals for timely preventive intervention in terms of replacement of the ascending aorta. State-of-the-art genetic testing is especially powerful in making the right diagnosis. However, while for young patients genetic testing is widely accepted, the benefit of genetic testing for older group of patients is unknown. Our study assesses the impact of age on the identification of patients at risk for hereditary aortopathy after replacement surgery of the ascending aorta.
Methods: A total of 207 on average 62-year-old patients (142 males and 65 females) who underwent replacement surgery of ascending aorta due to aneurysm or dissection have been evaluated by specialists in human genetics to find out which patient may qualify for genetic testing. Qualified patients and their relatives were invited to genetic counselling, which finally resulted in the decision whether or not genetic testing is needed. After patients provided informed consent, comprehensive genetic testing of genomic DNA derived from aorta or EDTA blood sample was performed, including, but not restricted to, the genes ACTA2, BGN, COL1A1, COL3A1, COL5A1, FBN1, FLNA, FOXE3, LOX, MAT2A, MFAP5, MYH11, MYLK, PRKG1, SKI, SLC2A10, SMAD2, SMAD3, TGFB2, TGFB3, TGFBR1, and TGFBR2.
Results: A total of 64 (31%) on average 54-year-old patients (46 males and 18 females) have qualified for genetic testing. While in 58 cases mutation analysis is still ongoing, in six cases genetic testing revealed the disease-causing mutation. Three patients (age at surgery 37, 43, 58 years) are carrier of a mutation in the gene FBN1, which is responsible for Marfan syndrome, two patients (age at surgery 56, 75 years) have a mutation of the gene COL3A1, which results in Ehlers-Danlos syndrome type IV, and one patient (age at surgery 41 years) carries mutation of the TGFBR1 gene, which is associated with Loeys-Dietz syndrome.
Conclusion: Our study provides new insight into the age of patients who underwent replacement surgery of the ascending aorta and qualified for mutation analysis. Accordingly, patient age does not exclude a genetic cause of the aortopathy and hence genetic testing should be offered to even older group of qualified patients.
