Turner Syndrome Work-Up
Initial Diagnostic Confirmation
All patients suspected of having Turner syndrome require karyotype analysis as the definitive diagnostic test, which should be performed promptly when clinical features suggest the diagnosis. 1
Clinical Indications for Karyotype Testing
Obtain karyotype analysis for any female presenting with: 2
- Unexplained short stature (height <5th percentile or falling off growth curve)
- Lymphedema at birth or in infancy (present in 97% of infants diagnosed with Turner syndrome)
- Delayed or absent puberty/primary amenorrhea
- Webbed neck (pterygium colli)
- Coarctation of the aorta or other congenital heart defects
- Two or more dysmorphic features including: high arched palate, nail dysplasia, short fourth metacarpal, strabismus, low posterior hairline, micrognathia, or retrognathia 3, 2
Growth Assessment Tool
Calculate the difference between target height and patient height standard deviation scores—a significant discrepancy serves as a simple, inexpensive screening tool for Turner syndrome even when somatic features are subtle. 3
Cardiovascular Evaluation (Mandatory at Diagnosis)
Comprehensive cardiovascular imaging is required at the time of diagnosis due to the significantly elevated risk of structural heart disease and aortic dissection. 4, 5
Baseline Cardiac Imaging
- Cardiac MRI is the preferred initial imaging modality to precisely measure aortic diameters throughout the entire aorta and identify congenital cardiovascular abnormalities that may be missed on echocardiography 6, 5
- Transthoracic echocardiography (TTE) to evaluate for:
Aortic Size Index Calculation (for patients ≥15 years)
Calculate the Aortic Size Index (ASI) to account for the typically smaller body size in Turner syndrome: 6, 5
- ASI = aortic diameter (mm) / body surface area (m²)
- Alternative: Aortic Height Index (AHI) = aortic diameter (mm) / height (m)
Risk stratification based on ASI: 6
- Low risk: ASI ≤2.0 cm/m² with no additional cardiovascular risk factors
- Moderate risk: ASI 2.0-2.3 cm/m²
- High risk: ASI >2.3 cm/m²
Laboratory Testing
Comprehensive metabolic and endocrine screening is recommended at diagnosis to identify associated comorbidities. 8
Initial Laboratory Panel
Obtain the following tests: 8
- Complete blood count (CBC) with differential to detect thrombocytopenia and cytopenias
- Thyroid-stimulating hormone (TSH) to screen for autoimmune thyroid disease
- Calcium and magnesium (including pH-corrected ionized calcium)
- Creatinine to assess renal function
- Lipid profile to evaluate cardiovascular risk
- Glucose and HbA1c to screen for diabetes (higher prevalence in Turner syndrome)
- Parathyroid hormone (PTH) if calcium abnormalities are detected
Additional Baseline Assessments
- Renal ultrasound to evaluate for structural renal abnormalities (horseshoe kidney, duplicated collecting system) 7
- Hearing evaluation due to increased risk of recurrent otitis media and sensorineural hearing loss 9
Surveillance Imaging Schedule
For Patients WITHOUT Additional Risk Factors
For Patients WITH Risk Factors
Risk factors include: bicuspid aortic valve, aortic coarctation, ASI >2.3 cm/m², hypertension, or aortic dilation. 6
- Annual surveillance imaging is required 4, 6
- More frequent imaging (every 6 months) if ASI is increasing or approaching surgical thresholds 4
Surveillance Laboratory Testing Schedule
Based on cardiovascular risk stratification: 8
- Low risk: Every 2-3 years
- Moderate risk: Annually
- High risk: Every 6-12 months
Karyotype Interpretation
Approximately 45% of patients have classic 45,X monosomy, while 55% have mosaicism or structural X chromosome abnormalities. 3, 9
Important: Even mosaic karyotypes with a minority of 45,X cells (e.g., 21% in 45,X/48,XXXX/46,XX mosaicism) require full Turner syndrome cardiovascular protocols, as the presence of any 45,X cells confers cardiovascular risk. 6
Phenotype-Karyotype Correlations
Classic 45,X monosomy is associated with: 9
- Universal short stature
- 100% primary amenorrhea
- Higher prevalence of cardiovascular abnormalities (OR 3.50)
Mosaic or structural X abnormalities may present with: 9
- Less severe short stature (77.8% affected)
- Primary amenorrhea in 63.2% (remainder have secondary amenorrhea)
- Lower but still significant cardiovascular risk
Common Pitfalls to Avoid
- Delayed diagnosis: The average delay from falling below the 5th percentile for height to diagnosis is 7.7 years; maintain high clinical suspicion and obtain karyotype early 2
- Relying on physical examination alone: Bicuspid aortic valve is often not detected by examination and requires echocardiography 7
- Failing to index aortic measurements: Standard reference ranges without body size adjustment lead to underestimation of cardiovascular risk 8, 6
- Overlooking subtle dysmorphic features: Not all patients present with classic features; some have minimal phenotypic manifestations 3
- Neglecting metabolic screening: Diabetes and dyslipidemia have higher prevalence in Turner syndrome and require systematic screening 8
- Using standard growth charts: Turner-specific growth charts should be used for monitoring 3
Blood Pressure Management
Aggressive hypertension control is critical throughout life, as hypertension is a major risk factor for aortic dissection. 6, 5
- Monitor blood pressure at every clinical encounter 4
- Consider beta-blockers and/or angiotensin receptor blockers (ARBs) to inhibit aortic growth, similar to Marfan syndrome management 6
Pre-Pregnancy Evaluation (If Applicable)
Mandatory comprehensive cardiovascular assessment before attempting pregnancy, as pregnancy significantly increases aortic dissection risk. 6, 5
Pregnancy is contraindicated if: 6
- ASI >2.5 cm/m²
- Any significant aortic dilation
- Bicuspid aortic valve with any aortic enlargement
- Aortic coarctation
- Uncontrolled hypertension