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Familial thoracic aortic aneurysm and dissection

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A 45-year-old man with no syndromic features has aortic root dilation. Family history reveals multiple relatives with aortic aneurysms or sudden death.

AD; ~20% of thoracic aortic disease is familial

  • Genes: ACTA2 (most common), MYH11, MYLK, PRKG1, SMAD3, TGFBR1/2
  • Non-syndromic aortic aneurysm/dissection
  • Variable penetrance
  • May have livedo reticularis, iris flocculi (ACTA2)
  • Patent ductus arteriosus (MYH11)
  • Aortic imaging (transthoracic echo, then CT or MR angiography) demonstrating thoracic aortic aneurysm or dissection, with a family history of aortic disease/sudden death
  • Gene panel testing (ACTA2, MYH11, MYLK, PRKG1, SMAD3, TGFBR1/2, FBN1); also evaluates for syndromic aortopathies such as Marfan and Loeys-Dietz
  • Cascade screening with aortic imaging in first-degree relatives; baseline imaging even when genetic cause is unidentified
  • Serial aortic imaging surveillance; interval set by aortic diameter, growth rate, and gene (more aggressive for TGFBR1/2, SMAD3, ACTA2)
  • Blood-pressure control with beta-blockers and/or angiotensin receptor blockers to reduce aortic wall stress
  • Prophylactic aortic root/ascending aortic surgery at diameter thresholds, lowered for high-risk genotypes and rapid growth
  • Avoid isometric/heavy resistance exercise and competitive/contact sports

Syndromic causes, "Thor is MALE": The 4 main syndromic causes of thoracic aortic disease are Marfan, ACTA2, Loeys-Dietz, and vascular EDS

This diagram organizes the causes of TAAD into syndromic (connective tissue) and non-syndromic (vascular smooth muscle) categories.

TAAD classification: syndromic causes (Marfan/FBN1, Ehlers-Danlos, Loeys-Dietz) vs non-syndromic causes (ACTA2, MYLK, MYH11, PRKG1) organized by actin and myosin pathways
TAAD classification: syndromic causes (Marfan/FBN1, Ehlers-Danlos, Loeys-Dietz) vs non-syndromic causes (ACTA2, MYLK, MYH11, PRKG1) organized by actin and myosin pathways

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