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

Abstract

Conclusion: Thoracic aortic aneurysms (TAAs) are frequently familial, with an autosomal dominant pattern of inheritance and a growth rate higher rate than that in nonfamilial TAAs. Summary: The authors studied phenotypic and genetic patterns of TAAs and dissections. The authors identified 520 patients with TAA and examined their pedigrees to identify family members with aneurysms. Patients were examined for age of presentation, familial clustering of aneurysms, rate of aneurysm growth, and hypertension as well as a correlation of aneurysm sites among kindred and pedigree inheritance patterns. There was an inherited pattern for TAA in 21.5% of non-Marfan patients. This pattern was primarily autosomal dominant (76.9%), with varying degrees of expression and penetrance. Patients with familial TAAs were younger than those with sporadically occurring TAAs (P < .0001), but was not as young as the Marfan patients (mean age, 58.2 vs 65.7 vs 27.4 years, P < .001. There were 197 patients with kindred aneurysms and TAA was present in 131 (66.5%). Abdominal aortic aneurysms (AAA) were present in 49 patients (24.9%), and 17 (8.6%) had either cerebral or other aneurysms. Hypertension and AAA were associated more with descending than ascending TAA (P < .001). The highest rate of aortic growth occurred in the patients with a familial pattern of TAA (0.21 cm/year). Growth was intermediate in patients with sporadically occurring TAA (0.16 cm/year). Aneurysm growth was lowest in the Marfan patients (0.1 cm/year, P < 0.01). Comment: A familial pattern of AAA has been long recognized. Surprisingly, relatively few previous studies have examined familial predisposition to TAA and thoracic aortic dissection. The important points of this article are that many TAAs and dissections are familial (20% of non-Marfan patients). In addition, patients with a familial pattern of TAA have a higher rate of aneurysm growth than those with sporadic disease. The data suggest screening for aneurysm disease in first-order relatives and probans of patients with TAA