thoracic aortic aneurysm
Friday 23 April 2010
ascending aortic aneurysms, dissecting aneurysm of thoracic aorta; ascending aortic aneurysm
fragmentation of elastic fibers
cystic medial change
thickening of the vasa vasorum
Both elastic fragmentation and cystic medial change are present in a high percentage of patients.
Cystic medial change is inversely correlated with increasing age of patients, especially in the group of patients without clinical evidence of Marfan’s syndrome.
Marked changes of these types in many younger patients without Marfan’s syndrome could reflect a "tissue insufficiency" in early life that causes the aortic wall to weaken and dilate.
Medial necrosis, fibrosis, and atherosclerosis are directly correlated with age. Hemodynamic events are considered to initiate injury and repair within the aortic wall.
Dissection is more frequently seen with medial abnormalities than with atherosclerosis.
- TGFB2-associated familial thoracic aortic aneurysms
- syphilitic aneurysm of the ascending aorta
TGFB2-associated familial thoracic aortic aneurysms
TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. (22772371)
- A predisposition for thoracic aortic aneurysms leading to acute aortic dissections can be inherited in families in an autosomal dominant manner.
- Genome-wide linkage analysis of two large unrelated families with thoracic aortic disease followed by whole-exome sequencing of affected relatives identified causative mutations in TGFB2.
- These mutations-a frameshift mutation in exon 6 and a nonsense mutation in exon 4-segregated with disease with a combined logarithm of odds (LOD) score of 7.7.
- Sanger sequencing of 276 probands from families with inherited thoracic aortic disease identified 2 additional TGFB2 mutations.
- TGFB2 encodes transforming growth factor (TGF)-β2, and the mutations are predicted to cause haploinsufficiency for TGFB2; however, aortic tissue from cases paradoxically shows increased TGF-β2 expression and immunostaining.
- Thus, haploinsufficiency for TGFB2 predisposes to thoracic aortic disease, suggesting that the initial pathway driving disease is decreased cellular TGF-β2 levels leading to a secondary increase in TGF-β2 production in the diseased aorta.
TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome.
Boileau C, Guo DC, Hanna N, Regalado ES, Detaint D, Gong L, Varret M, Prakash SK, Li AH, d’Indy H, Braverman AC, Grandchamp B, Kwartler CS, Gouya L, Santos-Cortez RL, Abifadel M, Leal SM, Muti C, Shendure J, Gross MS, Rieder MJ, Vahanian A, Nickerson DA, Michel JB; National Heart, Lung, and Blood Institute (NHLBI) Go Exome Sequencing Project, Jondeau G, Milewicz DM. Nat Genet. 2012 Jul 8;44(8):916-21. doi : 10.1038/ng.2348 PMID: 22772371