Table 6.

Selected Causes of Heritable Thoracic Aortic Disease (HTAD)

Gene/(Locus) 1, 2Proportion of HTAD Attributed to Mutation of GeneFindings
ACTA2 12%-21% 3In some: livido reticularis, iris flocculi, cerebral aneurysm, bicuspid aortic valve, & persistent patent ductus arteriosus
MYH11 1% 4Other cardiovascular finding: patent ductus arteriosus 5
MYLK 1% 6Aortic dissections w/minimal enlargement but limited experience; no associated features
PRKG1 1% 7Type A & B aortic dissections associated w/tortuosity & hypertension
MAT2A 1% 8Other cardiovascular finding: bicuspid aortic valve
FOXE3 1% 9Only affected males described; no associated features
MFAP5 < 1% 10Mild systemic features; associated w/lone paroxysmal atrial fibrillation
LOX 1% 11Associated w/bicuspid aortic valve, mild marfanoid features
(AAT1 or FAA1) 12UnknownMore diffuse vascular disease than in TAAD1, w/aneurysms affecting both thoracic & abdominal aorta & other arteries
(AAT2 or TAAD1) 12Unknown

Heritable thoracic aortic disease (HTAD) refers to thoracic aortic disease caused by mutation of a gene that confers a high risk for thoracic aortic aneurysms and aortic dissections (see Heritable Thoracic Aortic Disease Overview).


Locus is included when associated gene is not known.


TGFBR2 pathogenic variants all affecting the same codon (p.Arg460His and p.Arg460Cys) were found in four of 80 unrelated families with familial TAAD. Although the majority of vascular disease in these families involved ascending aortic aneurysms leading to type A dissections, affected family members also had characteristic findings of LDS including descending aortic disease and aneurysms of other arteries (e.g., cerebral, carotid, and popliteal arteries) and other connective tissue findings (e.g., pectus deformity and joint hypermobility). Furthermore, the identical TGFBR2 pathogenic variants reported in FTAAD have been observed in multiple families with typical features of LDS [Loeys et al 2006; Authors, unpublished data]. Currently, it is unclear whether a TGFBR2 pathogenic variant can lead to an isolated aortic aneurysm phenotype (i.e., FTAAD); thus, use of the term FTAAD to refer to families with TAAD and a heterozygous TGFBR2 pathogenic variant does not seem appropriate.


Guo et al [2015]. Two loci designated as AAT1 (FAA1) [Vaughan et al 2001] and AAT2 (TAAD1) [Guo et al 2001] are implicated in TAAD; the genes have not been identified.


From: Loeys-Dietz Syndrome

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