Familial thoracic aortic aneurysms and dissections - Incidence, modes of inheritance, and phenotypic patterns

Background. We examined the genetic nature and phenotypic features of thoracic aortic aneurysms ( TAAs) and dissections in a large cohort of patients. Methods. Interviews were conducted with 520 patients with TAAs and their pedigrees were compiled to identify family members with aneurysms. Study patients were divided into three groups: 101 non-Marfan patients, in 88 pedigrees, had a family pattern for TAA ( familial group), 369 had no family pattern ( sporadic group), and 50 had Marfan syndrome ( MFS). We determined incidence of familial clustering, age at presentation, rate of aneurysm growth, incidence of hypertension, correlation of aneurysm sites among kindred, and pedigree inheritance patterns. Results. An inherited pattern for TAA was present in 21.5% of non-MFS patients. The predominant inheritance pattern was autosomal dominant ( 76.9%), with varying degrees of penetrance and expressivity. The familial TAA group was significantly younger than the sporadic group ( p < 0.0001), but not as young as the MFS group ( p < 0.0001) ( mean ages, 58.2 versus 65.7 versus 27.4 years). Among all 197 probands and kindred with aneurysm, 131 ( 66.5%) had TAA, 49 ( 24.9%) had abdominal aortic aneurysm ( AAA), and 17 ( 8.6%) had cerebral or other aneurysms. Ascending aneurysm paired most commonly with ascending, and descending with abdominal. Abdominal aortic aneurysms ( AAAs) and hypertension were more often associated with descending than with ascending TAAs ( p < 0.001). Aortic growth rate was highest for the familial group ( 0.21cm/y), intermediate for the sporadic group ( 0.16 cm/y), and lowest for the Marfan group ( 0.1 cm/y; p < 0.01). Conclusions. TAAs are frequently familial diseases. The predominant mode of inheritance is autosomal dominant. Familial TAAs have a relatively early age of onset. Aneurysms in relatives may be seen in the thoracic aorta, the abdominal aorta, or the cerebral circulation. Screening of first-order relatives of probands with TAA is essential. Familial TAAs tend to grow at a higher rate, exemplifying a more aggressive clinical entity.