When should you screen for aortic aneurysm with hereditary conditions?

Screening for Aortic Aneurysms in Hereditary Conditions

Aortic imaging is recommended for all first-degree relatives of patients with thoracic aortic aneurysm and/or dissection to identify those with asymptomatic disease, regardless of age. 1, 2

Screening Recommendations by Condition

Syndromic Hereditary Thoracic Aortic Disease (HTAD)

Marfan Syndrome

• Initial comprehensive imaging at diagnosis
• Follow-up transthoracic echocardiography (TTE):
  • At least annually for aortic root diameter <45 mm without risk factors
  • Every 6 months for aortic root diameter <45 mm with risk factors
  • Every 6-12 months for aortic root diameter ≥45 mm 1
• Complete peripheral vascular and thoracoabdominal aorta imaging by CMR or CCT at first evaluation 1

Loeys-Dietz Syndrome

• More aggressive screening due to higher risk of dissection at smaller diameters
• Earlier surgical intervention may be recommended (at aortic diameter of 4.2 cm) 2

Vascular Ehlers-Danlos Syndrome (vEDS)

• Regular vascular surveillance of the aorta and peripheral arteries by DUS, CCT, or CMR 1

Turner Syndrome

• Use ascending aortic size index (ASI), aortic height index (AHI), or aortic z-score to define degree of aortic dilatation
• Imaging intervals based on estimated risk for dissection 1

Non-Syndromic HTAD with Identified Pathogenic Variant

• If a pathogenic variant (FBN1, TGFBR1, TGFBR2, COL3A1, ACTA2, MYH11) is identified in a patient:
  • First-degree relatives should undergo genetic counseling and testing
  • Only relatives with the genetic mutation should undergo aortic imaging 1
• Sequencing of ACTA2 gene is reasonable in patients with family history of thoracic aortic aneurysms/dissections 1
• Sequencing of other genes (TGFBR1, TGFBR2, MYH11) may be considered in patients with family history and clinical features associated with mutations in these genes 1

Positive Family History but No Identified Syndrome or Pathogenic Variant

• First-degree relatives should undergo TTE screening 2
• If TTE visualization is inadequate, proceed to CT angiography (CTA) or MR angiography (MRA) 2
• Follow-up based on findings:
  • No aortic dilation: repeat imaging in 5 years
  • Mild dilation: every 2-3 years
  • Moderate dilation: annual imaging
  • Severe dilation: every 6-12 months 2

Second-Degree Relatives

• If one or more first-degree relatives of a patient with known thoracic aortic aneurysm/dissection are found to have thoracic aortic dilatation, aneurysm, or dissection, imaging of second-degree relatives is reasonable 1

Special Considerations

Age-Related Screening

• For individuals with risk factors for HTAD but no identified pathogenic variant, imaging screening should begin at age 25 or 10 years below the youngest case in the family, whichever is younger 1
• For children with genetic syndromes associated with aortic disease, screening should begin at diagnosis

Bicuspid Aortic Valve-Associated Aortopathy

• CCT or CMR of entire thoracic aorta recommended at first diagnosis
• Annual measurement if aortic diameter >45 mm or increase >3 mm/year
• For BAV patients with maximum aortic diameter >40 mm, surveillance imaging by TTE after 1 year, then every 2-3 years if stable 1

Important Caveats

1. Normal imaging does not rule out disease: A substantial number of potential carriers may have normal aortic dimensions, especially at younger ages 3. Research shows that screening with aortic imaging does not detect all potential carriers of the disease.

2. Growth rates vary by condition: Familial thoracic aortic aneurysms tend to grow at a higher rate (0.21-0.22 cm/year) compared to sporadic cases (0.03-0.16 cm/year) and Marfan syndrome (0.1 cm/year), representing a more aggressive clinical entity 4, 5.

3. Inheritance patterns: The predominant mode of inheritance for familial thoracic aortic aneurysms is autosomal dominant (76.9%), but with varying degrees of penetrance and expressivity 4. This means some family members may carry the genetic mutation without showing symptoms.

4. Multi-site aneurysms: Relatives of patients with thoracic aortic aneurysms may develop aneurysms in other locations, including abdominal aorta or cerebral circulation 4, 5, necessitating comprehensive vascular assessment.

By implementing these screening recommendations, clinicians can identify individuals at risk for aortic complications early, allowing for appropriate medical management, surveillance, and timely surgical intervention to prevent potentially fatal aortic dissection or rupture.