What is the diagnostic approach for a patient suspected of having Marfan syndrome with a Ghent score > 7, particularly in pediatric patients?

Diagnostic Approach for Suspected Marfan Syndrome with Ghent Score > 7

Yes, all patients with a systemic score ≥7 should undergo both transthoracic echocardiography and dilated ophthalmologic examination, as these are essential to identify the two cardinal features of Marfan syndrome—aortic root dilation and ectopia lentis—which are required for definitive diagnosis. 1

Understanding the Revised Ghent Nosology Framework

The revised Ghent criteria fundamentally shifted the diagnostic paradigm by prioritizing aortic root aneurysm and ectopia lentis as the cardinal clinical features of Marfan syndrome. 2 A systemic score ≥7 alone does not establish the diagnosis—it must be combined with either aortic root dilation (Z-score ≥2) OR ectopia lentis OR a pathogenic FBN1 mutation to meet diagnostic criteria. 3, 1

The systemic score is only diagnostically meaningful when paired with objective cardiovascular or ocular findings, which is why both echocardiography and ophthalmology evaluations are mandatory. 3

Required Diagnostic Workup for Systemic Score ≥7

Cardiovascular Evaluation (Mandatory)

• Transthoracic echocardiography must measure: 1

  • Aortic annulus dimensions
  • Sinuses of Valsalva (most critical measurement)
  • Sinotubular junction
  • Proximal ascending aorta
  • Left ventricular function
  • Aortic regurgitation severity
  • Mitral valve prolapse and regurgitation
  • Tricuspid valve abnormalities

• Complete vascular imaging with cardiac MRI or CT from head to pelvis is required at initial evaluation to visualize the entire aorta beyond the root and assess peripheral vasculature. 1 This is particularly important as aortic complications can occur throughout the entire aorta, not just the root.

Ophthalmologic Evaluation (Mandatory)

• A dilated eye examination by an ophthalmologist is essential to definitively identify or exclude ectopia lentis, which is one of the two cardinal features required for diagnosis. 1, 4 This cannot be adequately assessed without pupillary dilation and specialized equipment.

• Ectopia lentis is typically present in Marfan syndrome but absent in Loeys-Dietz syndrome, making this a critical differentiating feature. 4

Diagnostic Algorithm Based on Findings

If Systemic Score ≥7 + Aortic Root Dilation (Z-score ≥2):

• Diagnosis of Marfan syndrome is confirmed without family history. 3
• Initiate annual echocardiography if root <4.5 cm and growth rate <0.5 cm/year. 3
• Begin beta-blocker therapy immediately. 3

If Systemic Score ≥7 + Ectopia Lentis:

• Diagnosis of Marfan syndrome is confirmed if aortic root is also dilated. 3
• If aortic root is normal, consider FBN1 genetic testing to establish diagnosis. 3

If Systemic Score ≥7 + Normal Echo + No Ectopia Lentis:

• Diagnosis of Marfan syndrome cannot be made based on systemic features alone. 3
• Consider FBN1 molecular genetic testing, particularly in children where age-dependent penetrance makes clinical diagnosis challenging. 1
• Repeat echocardiogram every 2-3 years until adult height is reached, as aortic root dilation may develop later. 3

Special Considerations in Pediatric Patients

Diagnosing Marfan syndrome in children is particularly challenging because penetrance of key features is age-dependent. 5 In pediatric patients younger than 20 years with a positive family history, aortic root dilation must exceed three standard deviations (Z-score >3) rather than two to meet diagnostic criteria. 3

• Aortic root dilation is usually present in early childhood and serves as an objective indicator, though the rate of increase is often greater than predicted based on body surface area. 6
• Mitral valve prolapse is common in children with Marfan syndrome, and mitral regurgitation requiring valve replacement is the leading cause of cardiovascular morbidity in childhood. 6
• The Kid-Short Marfan Score (Kid-SMS) identified significantly more suspected pediatric patients compared to Ghent nosology alone, suggesting standard criteria may miss cases in children. 7

Critical Pitfalls to Avoid

• Never rely on systemic score alone without objective cardiovascular and ophthalmologic assessment—this leads to misdiagnosis. 2
• Do not use symptom-based assessment for ectopia lentis; only dilated ophthalmologic examination by a specialist can definitively identify or exclude this finding. 1
• Avoid applying adult thresholds in children—different Z-score cutoffs apply based on age and family history. 3
• Do not assume a normal baseline echocardiogram excludes future diagnosis—regular surveillance is required as aortic dilation may develop over time, particularly in children. 3, 8

Differential Diagnoses Requiring Alternative Workup

If the complete workup does not support Marfan syndrome, consider: 1

• Loeys-Dietz syndrome (requires TGFBR1/TGFBR2 genetic testing)
• Hypermobile Ehlers-Danlos syndrome
• MASS phenotype (mitral valve, aorta, skeleton, skin)
• Ectopia lentis syndrome
• Familial thoracic aortic aneurysm syndromes

Molecular genetic testing for FBN1 mutations should be considered when clinical criteria remain equivocal after complete workup, as current testing successfully detects mutations in 90-95% of unequivocal cases. 3, 1