What is the most appropriate next step in management for a paediatric boy with failure to thrive, low-set ears, hypertelorism, webbed neck, and pulmonary stenosis?

Refer to Cardiology and Pursue Genetic Testing

The most appropriate next step is to refer this child to cardiology for management of pulmonary stenosis and simultaneously pursue genetic testing, as the constellation of dysmorphic features (low-set ears, hypertelorism, webbed neck) combined with pulmonary stenosis and failure to thrive strongly suggests Noonan syndrome or a related RASopathy. 1

Clinical Reasoning

Recognition of Noonan Syndrome Features

This patient presents with the classic triad that defines Noonan syndrome:

• Cardiac abnormalities: Pulmonary stenosis is the most common congenital heart defect in Noonan syndrome, occurring in approximately one-third of patients 1
• Characteristic dysmorphic features: Low-set ears, hypertelorism (widely spaced eyes), and webbed neck are pathognomonic facial features 1, 2
• Growth abnormalities: Failure to thrive and proportionate short stature are cardinal features 1

The American College of Cardiology/American Heart Association guidelines specifically identify this phenotypic presentation—describing patients with Noonan syndrome as having "short stature, webbed neck, hypertelorism, lymphedema, low-set ears and hairlines, hyperelastic skin, chest deformities, and micrognathia" in association with pulmonary stenosis 1

Why Cardiology Referral is Essential

Immediate cardiology evaluation is critical because:

• Pulmonary stenosis in Noonan syndrome patients shows lower success rates with balloon valvuloplasty compared to isolated pulmonary stenosis, particularly when dysplastic (thickened, immobile) valves are present 1
• The American Heart Association recommends that children with structural heart defects receive coordinated multidisciplinary care through a medical home model 3
• Cardiac catheterization may be necessary to assess the severity and determine optimal intervention timing, though echocardiography is typically the initial diagnostic modality 1
• Intervention is generally indicated when the resting gradient exceeds 40 mmHg, though patients with dysplastic valves (common in Noonan syndrome) may require surgical rather than catheter-based intervention 1

Why Genetic Testing is Equally Important

Genetic confirmation should occur concurrently because:

• The American Heart Association guidelines state that "genetic testing with counseling can be useful for children with IPAH or in families with heritable PAH to define the pathogenesis, to identify family members at risk, and to inform family planning" 1
• Noonan syndrome is caused by mutations in PTPN11 (50%), SOS1 (13%), RAF1 (5%), RIT1 (5%), or other genes in the RAS/MAPK pathway 1
• Specific PTPN11 mutations (particularly codon 61 or T73I) confer an 8-fold increased risk for various malignancies including acute lymphoblastic leukemia, neuroblastoma, and rhabdomyosarcoma 1
• Certain mutations carry high risk for juvenile myelomonocytic leukemia (JMML), requiring surveillance with physical examination and complete blood count with differential every 3-6 months until age 5 years 1
• Early genetic diagnosis enables appropriate cancer surveillance protocols and informs family planning 1

Why Other Options Are Inadequate

Endocrinology Referral Alone (Option B)

While growth hormone deficiency can occur in Noonan syndrome, referring solely to endocrinology would be inappropriate because:

• The failure to thrive in this context is more likely multifactorial, related to cardiac dysfunction, feeding difficulties from pulmonary stenosis, and the underlying genetic syndrome rather than isolated growth hormone deficiency 1
• The cardiac pathology requires immediate attention and takes precedence over growth evaluation 1
• Growth hormone therapy in Noonan syndrome patients with hypertrophic cardiomyopathy can be contraindicated, making cardiac assessment essential before any endocrine intervention 1

Gastroenterology Referral (Option C)

Gastroenterology referral would miss the diagnosis entirely because:

• The failure to thrive is not primarily a gastrointestinal problem but rather secondary to cardiac disease and the underlying genetic syndrome 1
• The presence of multiple dysmorphic features and cardiac pathology mandates evaluation for a syndromic diagnosis first 1
• Feeding problems in Noonan syndrome infants are typically related to hypotonia, cardiac dysfunction, and structural abnormalities rather than primary GI pathology 1

Critical Management Considerations

Additional Evaluations to Coordinate

Once cardiology and genetics are engaged, the following should be systematically addressed:

• Hematologic screening: Obtain complete blood count, platelet count, platelet function studies, and von Willebrand screen before any surgical intervention, as bleeding diathesis occurs in Noonan syndrome 1
• Ophthalmologic evaluation: Screen for ptosis, amblyopia, refractive errors, and strabismus 1
• Audiology assessment: Evaluate for sensorineural hearing loss, which occurs in up to 40% of patients 1, 4
• Renal ultrasound: Screen for structural renal anomalies 1
• Developmental assessment: Evaluate for learning difficulties and arrange early intervention services as needed 1

Common Pitfalls to Avoid

• Do not delay cardiac evaluation while pursuing genetic testing—both should proceed simultaneously 1
• Do not assume isolated pulmonary stenosis—the presence of dysmorphic features mandates syndromic evaluation 1
• Do not proceed with cardiac intervention without hematologic screening—bleeding complications are significantly increased in Noonan syndrome 1
• Do not overlook cancer surveillance if specific high-risk mutations are identified on genetic testing 1