What is the recommended treatment approach for a patient with a Turner syndrome variant?

Management of Turner Syndrome Variants

All patients with Turner syndrome variants require comprehensive cardiovascular evaluation at diagnosis with both transthoracic echocardiography (TTE) and cardiac MRI, followed by risk-stratified surveillance and consideration for prophylactic aortic surgery when the aortic size index (ASI) reaches ≥2.5 cm/m² in the presence of risk factors. 1

Initial Diagnostic Evaluation

At the time of diagnosis, perform both TTE and cardiac MRI to evaluate for:

• Bicuspid aortic valve (BAV), present in 15-30% of patients 1
• Aortic root and ascending aortic dilation (33% prevalence) 1
• Aortic coarctation (7-18% prevalence) 1
• Other congenital heart defects 1

The cardiovascular evaluation is critical because 50% of Turner syndrome patients have cardiovascular defects, and 85% of aortic dissections occur in the ascending aorta at relatively small absolute diameters due to short stature. 1

Risk Stratification Using Aortic Size Index

For patients ≥15 years old, calculate the ASI by dividing maximal aortic diameter (cm) by body surface area (m²): 1, 2

• ASI >2.0 cm/m² is abnormal 2
• ASI >2.3 cm/m² indicates increased dissection risk requiring annual surveillance 1
• ASI ≥2.5 cm/m² with risk factors warrants surgical consideration 1

For children <15 years old, use Turner syndrome-specific z-scores instead of ASI. 2, 3

This indexing approach is essential because Turner syndrome patients may experience aortic dissection at small absolute aortic diameters that would be considered safe in the general population. 1

Surveillance Imaging Protocol

Without risk factors for aortic dissection (no BAV, coarctation, hypertension, or significant dilation): 1

• Children: TTE or MRI every 5 years 1, 3
• Adults: TTE or MRI every 10 years 1, 3
• Before planning pregnancy 1

With ASI >2.3 cm/m²:

• At least annual surveillance imaging 1, 2

With risk factors for aortic dissection (BAV, coarctation, hypertension):

• Surveillance interval depends on aortic diameter, ASI, and aortic growth rate 1, 3
• More frequent monitoring as ASI approaches 2.5 cm/m² 2

The 2022 ACC/AHA guidelines emphasize that cardiac MRI is particularly important because aortopathy frequently involves the mid-ascending aorta, which may not be reliably visualized on TTE alone. 1

Surgical Intervention Thresholds

Prophylactic aortic root/ascending aorta replacement is reasonable when: 1

• ASI ≥2.5 cm/m² AND risk factors present (BAV, coarctation, hypertension) - Class IIa recommendation 1, 4
• ASI ≥2.5 cm/m² without risk factors - may be considered (Class IIb) 1

Critical consideration: Measurements must account for the patient's stature using Turner-specific normative data or ASI calculation. 1 In obese patients or those with low body weight relative to height, an absolute aortic diameter >4.0 cm may be more accurate than ASI for determining dissection risk. 2

Hypertension Management

Treat hypertension aggressively according to general guidelines: 4

• Consider beta-blockers and/or ARBs to potentially inhibit aortic growth 4
• Hypertension is a major modifiable risk factor for aortic dissection 1

Pregnancy Considerations

Pregnancy in Turner syndrome carries substantial aortic dissection risk and requires: 1

• Mandatory thorough cardiovascular evaluation before attempting pregnancy 4
• Extensive pre-conception counseling 4
• Risk is especially elevated with pre-existing BAV or aortic abnormalities 1
• Often requires assisted reproductive technology 1

The 2018 AHA/ACC guidelines note that pregnancy-related dissection risk is particularly concerning, making pre-pregnancy cardiovascular assessment non-negotiable. 1

Multidisciplinary Management Beyond Cardiovascular Care

Screen for and manage associated conditions: 5, 6

• Hypothyroidism - regular screening required 4
• Glucose intolerance and diabetes mellitus 7, 5
• Osteoporosis - bone mineral density monitoring 7, 5
• Liver dysfunction and hyperlipidemia 7
• Hearing impairment 7

Growth and hormone therapy:

• Growth hormone therapy for short stature 5, 6
• Hormone replacement therapy for ovarian dysgenesis and premature menopause 5, 6, 8

Psychosocial support and genetic counseling should be offered to all patients. 4, 6

Critical Pitfalls to Avoid

Do not use absolute aortic diameters without indexing to body size - this systematically underestimates dissection risk in Turner syndrome patients due to their short stature. 2, 3

Do not rely solely on TTE - the mid-ascending aorta requires cardiac MRI or CT for adequate visualization. 1

Do not fail to screen for associated comorbidities - the multisystem nature of Turner syndrome means isolated cardiovascular management is insufficient. 4, 7

Do not delay diagnosis - despite a conspicuous phenotype, average age at diagnosis is around 15 years, representing missed opportunities for early intervention. 5