What is the diagnosis and management for a patient with low-set ears, webbed neck, and a cardiac murmur, suspected of having a genetic syndrome such as Turner syndrome or Noonan syndrome?

Immediate Diagnostic Workup and Management

Order karyotype analysis immediately to confirm the diagnosis, as the clinical triad of low-set ears, webbed neck, and cardiac murmur strongly suggests either Turner syndrome (if female) or Noonan syndrome (either sex), both requiring urgent cardiovascular evaluation and syndrome-specific management. 1, 2, 3

Initial Diagnostic Approach

Confirm the Genetic Diagnosis

• Karyotype analysis is the essential first step because it definitively distinguishes Turner syndrome from Noonan syndrome and detects mosaicism present in approximately 55% of Turner syndrome patients, which significantly influences prognosis and management 3, 4
• Karyotyping must identify any Y chromosome material in Turner syndrome patients, as this confers increased gonadoblastoma risk requiring gonadectomy 3
• If karyotype is normal (46,XX or 46,XY) but clinical features persist, proceed with targeted gene panel testing for Noonan syndrome (PTPN11, SOS1, RAF1, KRAS, RIT1) 1, 2, 5

Distinguish Between the Two Syndromes

Turner Syndrome (females only):

• 45,X karyotype with short stature, webbed neck, lymphedema, and cardiovascular defects including bicuspid aortic valve (15-30%), aortic coarctation (7-18%), and ascending aortic dilation (33%) 1, 3
• Primary amenorrhea and premature ovarian failure are characteristic 5

Noonan Syndrome (both sexes):

• Normal karyotype with webbed neck, hypertelorism, low-set ears, short stature, chest deformities, and pulmonary stenosis (most common cardiac defect in approximately one-third of patients) 1, 2, 6
• Bleeding diathesis and increased malignancy risk distinguish it from Turner syndrome 2, 6

Urgent Cardiovascular Evaluation

Immediate Cardiac Imaging

• Obtain transthoracic echocardiography (TTE) immediately to evaluate the cardiac murmur and screen for structural abnormalities 1, 3
• Cardiac MRI is recommended at the time of diagnosis to comprehensively evaluate for congenital heart defects and precisely measure aortic diameters, as echocardiography alone misses important structural abnormalities 1, 3

Turner Syndrome-Specific Cardiac Management

• Calculate the aortic size index (ASI = aortic diameter in cm ÷ BSA in m²) if patient is ≥15 years old, as absolute measurements critically underestimate dissection risk in patients with characteristically small stature 1, 3
• ASI >2.3 cm/m² requires at least annual surveillance imaging 1
• ASI ≥2.5 cm/m² with risk factors (hypertension, bicuspid aortic valve, coarctation) warrants consideration of prophylactic surgical intervention 1
• Aortic dissection is a major cause of premature death in Turner syndrome, with 85% occurring in the ascending aorta at younger ages and smaller diameters than the general population 1, 3

Noonan Syndrome-Specific Cardiac Management

• Immediate cardiology referral is critical because pulmonary stenosis in Noonan syndrome shows lower success rates with balloon valvuloplasty compared to isolated pulmonary stenosis, often requiring surgical intervention for dysplastic valves 2
• Intervention is generally indicated when the resting gradient exceeds 40 mmHg 2
• Hypertrophic cardiomyopathy is also common and requires specific surveillance 1, 6, 7

Additional Essential Evaluations

Pre-Procedural Assessment

• Obtain hematologic screening before any surgical intervention in suspected Noonan syndrome, as bleeding diathesis occurs frequently and must be identified prior to procedures 2, 6
• Preoperative coagulation studies are mandatory 6

Syndrome-Specific Surveillance

For Turner Syndrome:

• Measure blood pressure in all four extremities to screen for coarctation 5
• Renal ultrasound to screen for structural renal anomalies 2
• Establish lifelong cardiovascular surveillance: every 5 years in children without risk factors, every 10 years in adults without risk factors, and before planned pregnancy 1

For Noonan Syndrome:

• Ophthalmologic evaluation for ptosis, amblyopia, refractive errors, and strabismus 2, 8
• Audiologic assessment for sensorineural hearing loss (occurs in up to 40% of patients) 2, 6, 9
• Renal ultrasound for structural anomalies 2
• Developmental assessment for learning difficulties with early intervention services as needed 2, 6
• Cancer surveillance with physical examination and complete blood count with differential every 3-6 months until age 5 years for specific PTPN11 mutations conferring increased risk of acute lymphoblastic leukemia, neuroblastoma, rhabdomyosarcoma, and juvenile myelomonocytic leukemia 2

Critical Pitfalls to Avoid

• Do not delay karyotyping to pursue endocrine or other testing first—the diagnosis must be cytogenetically confirmed to guide all subsequent management 3
• Do not assume normal cardiovascular anatomy based on physical examination alone, as up to 50% of Turner syndrome patients and 80% of Noonan syndrome patients have cardiovascular defects requiring imaging to detect 1, 2, 3
• Do not use absolute aortic measurements without indexing to body size in Turner syndrome patients, as this underestimates dissection risk 1, 3
• Do not omit baseline cardiac MRI at diagnosis, as it provides critical information beyond echocardiography 1, 3
• Do not proceed with surgical procedures in Noonan syndrome without preoperative coagulation studies 2, 6

Counseling the Family

• Explain that genetic confirmation will occur concurrently with cardiac evaluation and enables appropriate surveillance protocols and informs family planning 2, 3
• Emphasize that with coordinated multidisciplinary care through a medical home model, the majority of children with these syndromes will grow up and function normally in the adult world 2, 6
• Discuss that signs and symptoms often lessen with age, and most adults do not require special medical care beyond syndrome-specific surveillance 6
• Address that autosomal dominant inheritance occurs in some families, though many cases are sporadic, and genetic counseling will clarify recurrence risk 6, 7