Aortic root dilation

A patient with an enlarged aortic root or ascending aorta on echo or cross-sectional imaging, or a family history of thoracic aortic dissection in a young relative. Z-score above +2 in a child or absolute diameter above population norms in an adult is the trigger. The clinical job is to decide whether this is a syndromic heritable thoracic aortic disease (HTAD), a non-syndromic familial TAAD, a bicuspid-valve-associated aortopathy, or part of a chromosomal disorder, because gene identity drives both surveillance interval and threshold for prophylactic root replacement.

Three questions structure the work-up:

1. Syndromic features? Skeletal (tall stature, arachnodactyly, pectus, scoliosis, arm-span exceeding height), ocular (ectopia lentis, myopia), craniofacial (hypertelorism, bifid uvula, cleft palate), skin (translucent, easy bruising, atrophic scars), arterial (tortuosity beyond the root, aneurysms elsewhere). Each cluster points to a different gene family.
2. Family history. Three generations including unexplained sudden death, dissection in someone under 60, aortic surgery, drowning, "heart attack" in the young. Many family members are asymptomatic until they dissect.
3. Imaging extent. Root only vs entire arterial tree. FBN1 disease tends to be root-focused; TGFBR1/2 and SMAD3 disease is "aortopathy everywhere," demanding head-to-pelvis imaging.

Syndromic HTAD

• Marfan syndrome (FBN1, AD): Ghent criteria diagnosis. Cardinal features are aortic root dilation/dissection + ectopia lentis. Skeletal score, family history, and systemic features make up the rest. Surveillance echo annually; prophylactic root replacement at ~5.0 cm (earlier with family history of dissection or rapid growth). Pregnancy management is its own chapter.
• Loeys-Dietz syndrome (TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3; AD): aortic disease throughout the arterial tree, not just the root. Hypertelorism + bifid uvula + cleft palate + arterial tortuosity + craniosynostosis (some subtypes) + thin translucent skin in others. Lower threshold to repair: ~4.4 cm in adults, smaller in children. Whole-body MRA at diagnosis and at intervals.
• Vascular Ehlers-Danlos syndrome (COL3A1, AD): thin translucent skin + characteristic facies (thin nose, thin lips, hollow cheeks, prominent eyes) + easy bruising + arterial, uterine, and bowel rupture. No prophylactic vascular surgery in most cases: operative complications are catastrophic. Manage medically (celiprolol), avoid pregnancy without specialist input, avoid invasive imaging when possible.
• Shprintzen-Goldberg syndrome (SKI, AD): Marfanoid + craniosynostosis + intellectual disability.

Non-syndromic familial TAAD

• Familial thoracic aortic aneurysm and dissection (ACTA2, MYH11, PRKG1, MYLK, LOX; AD): aortopathy without dysmorphism. ACTA2 is the most common; it also causes a syndrome of vascular disease that includes premature coronary disease, stroke, and smooth muscle dysfunction (livedo, mydriasis, PDA). PRKG1 is associated with early dissection.

Bicuspid aortic valve aortopathy

• Bicuspid aortic valve (BAV) is the most common congenital cardiac lesion (~1-2% of population). 9-21% have associated aortopathy. Mostly sporadic but with familial clustering; first-degree relatives warrant screening echo.

Chromosomal

• Turner syndrome (45,X): bicuspid valve (30-50%) + coarctation + aortic dilation + dissection (rare but devastating). All Turner patients need cardiac surveillance for life; pregnancy in Turner is high-risk for dissection.

1. Confirm and measure by TTE; cardiac MRA or gated CT to assess the rest of the thoracic and abdominal aorta.
2. Three-generation pedigree specifically asking about dissection, sudden death, drowning, "heart attack" before age 60, aortic surgery.
3. Targeted exam for syndromic features: arm-span/height ratio, wrist and thumb signs, pectus, scoliosis, palatal anomalies, uvula, skin, joint hypermobility, ocular lens position.
4. Slit-lamp exam for ectopia lentis (Marfan-specific cardinal feature).
5. HTAD gene panel (covers all the major syndromic and non-syndromic genes). Many panels also include connective tissue and bicuspid-valve genes.
6. Karyotype in any short female with aortic disease or unexplained bicuspid valve.
7. Cascade screening of first-degree relatives: echo + targeted variant testing once a familial variant is identified.