TABLE 7.
TAA Syndromes and Conditions Attributable to a Heritable or Genetic Cause
| Condition | Gene | Clinical Features |
|---|---|---|
| Syndromic HTAD * | ||
| Marfan syndrome | FBN1 | Aortic root aneurysm, aortic dissection, TAA, MVP, long bone overgrowth, arachnodactyly, dolichostenomelia, scoliosis, pectus deformities, ectopia lentis, myopia, tall stature, pneumothorax, dural ectasia |
| Loeys-Dietz syndrome | TGFBR1, TGFBR2, SMAD3, † TGFB2, TGFB3 | TAA, branch vessel aneurysms, aortic dissection, arterial tortuosity, MVP, craniosynostosis, hypertelorism, bluish sclera, bifid/broad uvula, translucent skin, visible veins, club feet, dural ectasia, and premature osteoarthritis and peripheral neuropathy† |
| Vascular Ehlers-Danlos syndrome | COL3A1 | TAA, AAA, arterial rupture, aortic dissection, MVP, bowel and uterine rupture, pneumothorax, translucent skin, atrophic scars, small joint hypermobility, easy bruising, carotid-cavernous fistula |
| Arterial tortuosity syndrome | SLC2A10 | Tortuous large and medium sized arteries, aortic dilation, craniofacial, skin and skeletal features |
| Shprintzen-Goldberg syndrome | SKI | Craniosynostosis, skeletal features, aortic dilation |
| Ehlers-Danlos syndrome with periventricular nodular heterotopia | FLNA | X-linked, periventricular nodular heterotopia, TAA, BAV, MV disease, PDA, VSD, seizures, joint hypermobility |
| Meester-Loeys syndrome | BGN | X-linked, TAA, aortic dissection, MV disease |
| LOX-related TAA | LOX | TAA, BAV, aortic dissection, Marfanoid habitus in some |
| Smooth muscle dysfunction syndrome | ACTA2 | TAA, moyamoya-like cerebrovascular disease, pulmonary hypertension, pulmonary disease, hypoperistalsis, hypotonic bladder, congenital mydriasis11 |
| Nonsyndromic HTAD (Familial TAA) | ||
| FTAA | ACTA2 | TAA, aortic dissection, premature CAD and moyamoya-like cerebrovascular disease, livedo reticularis, iris flocculi |
| FTAA | MYH11 | TAA, aortic dissection, PDA |
| FTAA | MYLK | Aortic dissection at relatively small aortic size |
| FTAA | PRKG1 | Aortic dissection at young ages at small aortic sizes |
| FTAA | MAT2A | TAA, aortic dissection, BAV |
| FTAA | MFAP5 | TAA, aortic dissection, skeletal features may be present |
| FTAA | FOXE3 | TAA, aortic dissection |
| FTAA | THSD4 | TAA, aortic dissection |
| Bicuspid Aortic Valve–Associated Ascending Aortic Aneurysm | ||
| Familial BAV/AS and TAA | NOTCH1 | Aortic valve stenosis, TAA |
| BAV with TAA | TGFBR2, MAT2A, GATA5, SMAD6, LOX, ROBO4, TBX20 | Syndromic and nonsyndromic HTAD and FTAA with an increased frequency of BAV |
| Turner syndrome | XO, Xp | BAV, CoA, TAA, aortic dissection, short stature, lymphedema, webbed neck, premature ovarian failure |
Some individuals with pathogenic variants in a gene that can lead to syndromic HTAD have very few or no syndromic features, and variants in some genes causing syndromic HTAD may also lead to nonsyndromic HTAD.
SMAD3 premature osteoarthritis and peripheral neuropathy.
AAA indicates abdominal aortic aneurysm; AS, aortic stenosis; BAV, bicuspid aortic valve; CAD, coronary artery disease; CoA, coarctation of the aorta; EDS, Ehlers-Danlos syndrome; FTAA, familial thoracic aortic aneurysm (and dissection) syndrome; HTAD, heritable thoracic aortic disease; MV, mitral valve; MVP, mitral valve prolapse; PDA, patent ductus arteriosus; TAA, thoracic aortic aneurysm; and VSD, ventricular septal defect.