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A child with hypertelorism, bifid uvula, and arterial tortuosity is found to have aortic root dilation at age 5. Unlike Marfan syndrome, he does not have lens dislocation.

AD; TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, TGFB3

  • TGF-β receptor variants → paradoxical increased TGF-β signaling
  • Craniofacial: Hypertelorism, bifid/broad uvula, cleft palate
  • Vascular: Arterial aneurysms/dissections throughout arterial tree (not just aorta), arterial tortuosity
  • Skeletal: Marfanoid features (but less prominent)
  • Other: Cervical spine instability, clubfoot
  • NO ectopia lentis (unlike Marfan)

Important: More aggressive vascular disease than Marfan - earlier surgery often needed

  • A pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, or TGFB3 in the setting of arterial aneurysm/dissection and characteristic craniofacial findings
  • Imaging extends beyond the aortic root: head-to-pelvis arterial imaging (CTA or MRA) is needed because aneurysms and tortuosity occur throughout the arterial tree, with echo for aortic root surveillance
  • Aggressive vascular surveillance with serial echo and whole-body arterial imaging
  • Prophylactic aortic surgery at smaller diameters than in Marfan syndrome, because dissection occurs at lower aortic dimensions
  • Beta-blockers or ARBs to reduce hemodynamic stress on the arterial wall
  • Activity restriction (avoid contact sports and isometric exertion)

"Loey's Diet": To remember the genes, think of "Loey's Diet": TGFB(R) = Too much Gluten Free BRead makes you SMAD (Super MAD / hangry). The genes are TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, SMAD3

"Lens OK in Loeys": Unlike Marfan, there is no ectopia lentis in Loeys-Dietz. "Lens Ok in Loeys"

This table compares the three main Marfanoid conditions (Marfan, homocystinuria, and Loeys-Dietz) by inheritance, gene, connective tissue defect, clinical features, and treatment.

Marfan vs homocystinuria vs Loeys-Dietz: key differences in inheritance (AD/AR/AD), genes (FBN1/CBS/TGFBR), lens dislocation direction, cleft palate, intellectual disability, and thromboembolism
Marfan vs homocystinuria vs Loeys-Dietz: key differences in inheritance (AD/AR/AD), genes (FBN1/CBS/TGFBR), lens dislocation direction, cleft palate, intellectual disability, and thromboembolism

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