Genetics links abdominal and thoracic aorta aneurysm

Abstract Introduction Familial disease, with a genetic cause, occurs in at least 20–30% of the families of patients with an aortic aneurysm. In these families there is an increased risk for relatives. Therefor family screening is recommended around the age of 50–60 years for first degree relatives of patients with an abdominal aneurysm (AAA) and relatives of patients with thoracic aorta aneurysms (TAA). However current guidelines do not specify the extend of aorta screening for relatives of patients with AAA and patients with TAA. Current practice is that first degree relatives of AAA patients are offered abdominal echo screening for AAA and relatives of TAA patients cardiologic echo for TAAA. Although co- occurrence of AAA with TAAA in rare genetic disease is well known, for other familial aneurysm disease, the frequency of the co-occurrence of AAA and TAAA has not been established. Purpose To improve family screening for familial aneurysm, and identify the role of underlying genetic defects. Methods To determine the genetics of AAA, whole exome sequencing and CT family screening of the complete aorta was performed in 391 families with familial aneurysm. These families are nested in a patient cohort ascertained form unselected consecutively diagnosed AAA patients visiting the Vascular Surgery Clinic at the our MC. Results In 391 families, 360 relatives had a dilated aorta. The spectrum of aortic features in the relatives included 210 (58%) relatives with AAA, 102 (28%) relatives with TAA. Co-occurrence of AAA and TAA was noted in 41 (11%) relatives. In addition 66 (18%) and 79 (22%) had a dilation in the arteria iliaca communis sinistra resp. dextra. In 18 families pathogenic mutations in 11 aneurysm genes were detected. Conclusion To reduce underdiagnoses of relatives of AAA patients, CT screening of the total aorta and the iliac arteries is the method of choice, and should replace echo screening of specific parts of the aorta in relatives. Updating the guidelines for family screening for aortic aneurysms is needed to improve early detection and treatment of family members with aorta dilatations. Acknowledgement/Funding Stichting Lijf en Leven