What is the initial test for screening Beckwith-Wiedemann syndrome (BWS)?

Screening for Beckwith-Wiedemann Syndrome

Alpha-fetoprotein (AFP) is the initial test for screening Beckwith-Wiedemann syndrome (BWS), along with abdominal ultrasound, as AFP screening is sensitive for hepatoblastoma and can detect elevations before ultrasound visualization. 1, 2

Comprehensive Screening Protocol

Initial Diagnosis

• Clinical features assessment: macroglossia, omphalocele/umbilical hernia, facial nevus flammeus, hemihyperplasia, and organ overgrowth
• Genetic testing to determine molecular subtype:
  • Methylation analysis of imprinting control regions (IC1 and IC2)
  • Assessment for paternal uniparental isodisomy (pUPD11)
  • CDKN1C mutation analysis

Tumor Surveillance Protocol

• For all BWS patients regardless of molecular subtype:

  • Renal ultrasound every 3 months from birth through age 7 years 1, 2
  • Full abdominal ultrasound every 3 months from birth through age 4 years 1
  • Serum AFP measurements every 3 months from birth through age 4 years 1, 2

• Additional surveillance based on molecular subtype:

  • Patients with CDKN1C mutations: urine catecholamines and chest radiographs to screen for neuroblastoma 1, 2

AFP Monitoring Guidelines

AFP is particularly important for hepatoblastoma screening, as BWS patients have a 2,280 times higher risk than the general population 1:

• AFP elevation often precedes detection by ultrasound 1
• Interpret AFP values in context of:
  • Age-appropriate reference ranges (BWS patients typically have higher baseline AFP)
  • Trend over time (expect declining values through infancy)
  • Recent imaging findings

AFP Result Interpretation

• Small rises within reference ranges: generally not concerning, may be due to intercurrent illness or teething
• Moderate elevations (50-100 ng/ml): repeat AFP in 6 weeks and review most recent ultrasound
• Large elevations (>1000 ng/ml): validate value and proceed to additional imaging (MRI) 1

Importance of Molecular Subtyping

Tumor risk varies significantly by molecular subtype 1, 2:

• IC1 gain of methylation: 28% risk (primarily Wilms tumor)
• pUPD11: 16% risk (mixed tumor types)
• CDKN1C mutations: 6.7% risk (including neuroblastoma)
• IC2 loss of methylation: 2.6% risk (lowest risk group)

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on molecular subtype to determine screening protocol. While European guidelines suggest tailored screening based on molecular subtype, US guidelines recommend uniform screening for all BWS patients due to documented cases of Wilms tumor in supposedly "low-risk" molecular subtypes 1, 3

• Pitfall: Misinterpreting elevated AFP in neonates. AFP values are naturally high in neonates and decline over the first year of life, with BWS patients often having higher baseline levels 1, 4

• Pitfall: Discontinuing surveillance too early. While most tumors occur in early childhood, cases have been documented up to age 8 years, necessitating continued surveillance 1

• Pearl: Regular physical examinations by specialists (geneticist or pediatric oncologist) twice yearly complement imaging surveillance and provide opportunity for family education 1

• Pearl: Tissue mosaicism can occur in BWS patients, potentially leading to false-negative genetic test results. If clinical suspicion remains high despite negative testing, consider testing additional tissue samples 5