MedGen

Any familial thoracic aortic aneurysm and aortic dissection in which the cause of the disease is a mutation in the ACTA2 gene. [from MONDO]

Any familial thoracic aortic aneurysm and aortic dissection in which the cause of the disease is a mutation in the MYH11 gene. [from MONDO]

Aneurysms and dissections of the aorta usually result from degenerative changes in the aortic wall. Thoracic aortic aneurysms and dissections are primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. In contrast, degeneration leading to abdominal aortic aneurysm (100070) is usually caused by a combination of factors including age, atherosclerosis, hypertension, and infectious, inflammatory, or autoimmune processes. Medial necrosis and thoracic aortic aneurysm/dissection are known to occur in certain connective tissue diseases such as Marfan syndrome (154700), and vascular (type IV) Ehlers-Danlos syndrome (130050). More commonly, however, medial necrosis occurs in the absence of a clearly identifiable syndrome. Genetic Heterogeneity of Thoracic Aortic Aneurysm Loci for isolated thoracic aortic aneurysm have been identified on chromosomes 11q (AAT1) and 5q (AAT2; 607087). Mutation in the MYH11 gene (160745) on chromosome 16p causes AAT4 (132900). Mutation in the ACTA2 gene (102620) on chromosome 10q causes AAT6 (611788). Mutation in the MYLK gene (600922) on chromosome 3q21 causes AAT7 (613780). Mutation in the PRKG1 gene (176894) on chromosome 10q11 causes AAT8 (615436). Mutation in the MFAP5 gene (601103) on chromosome 12p13 causes AAT9 (616166). Mutation in the LOX gene (153455) on chromosome 5q23 causes AAT10 (617168). Mutation in the FOXE3 gene (601094) on chromosome 1p33 causes susceptibility to AAT11 (617349). Thoracic aortic aneurysm with dissection (e.g., AAT3 and AAT5) can occur as a manifestation of the Loeys-Dietz syndrome (see LDS2, 610168 and LDS1, 609192, caused by mutation in the TGFBR2 (190182) and TGFBR1 (190181) genes, respectively). Reviews Pyeritz (2014) reviewed heritable thoracic aortic disorders with particular attention to causative genes, including components of the extracellular matrix, vascular smooth muscle cytoskeleton, and TGF-beta and other signaling pathways. [from OMIM]