Management Approach for Beckwith-Wiedemann Syndrome
Children with Beckwith-Wiedemann syndrome require standardized tumor surveillance with renal ultrasounds every 3 months from birth through age 7 and abdominal ultrasounds with alpha-fetoprotein measurements every 3 months through age 4 to detect early malignancies and improve survival outcomes.1
Clinical Characteristics and Diagnosis
Beckwith-Wiedemann syndrome (BWS) is a rare overgrowth syndrome with an incidence of approximately 1 in 10,500 births, characterized by:
- Pre- and postnatal constitutional and organ overgrowth
- Macroglossia (enlarged tongue)
- Omphalocele/umbilical hernia
- Facial nevus flammeus (port-wine stain)
- Hemihyperplasia (asymmetric growth)
- Predisposition to embryonal tumors 1
Diagnosis is based on clinical features and confirmed through molecular testing to identify the specific genetic or epigenetic abnormality affecting chromosome 11p15.
Genetic and Epigenetic Mechanisms
BWS results from dysregulation of growth genes on chromosome 11p15 through several mechanisms:
- Gain of methylation at imprinting control region 1 (IC1/H19/IGF2:IG-DMR)
- Loss of methylation at imprinting control region 2 (IC2/KCNQ1OT1:TSS-DMR)
- Paternal uniparental isodisomy (pUPD11)
- Mutations in CDKN1C gene
- Chromosomal rearrangements 1
The molecular subtype significantly impacts tumor risk:
- IC1 gain of methylation: 28% tumor risk (primarily Wilms tumor)
- pUPD11: 16% tumor risk
- CDKN1C mutations: 6.7% tumor risk
- IC2 loss of methylation: 2.6% tumor risk 1, 2
Tumor Surveillance Protocol
Wilms Tumor Screening
- Renal ultrasounds every 3 months from birth (or time of diagnosis) through the 7th birthday 1
- More frequent monitoring may be needed for high-risk molecular subtypes (IC1 gain of methylation)
Hepatoblastoma Screening
- Full abdominal ultrasound every 3 months from birth (or time of diagnosis) through the 4th birthday 1
- Serum alpha-fetoprotein (AFP) measurements every 3 months through age 4 1
Additional Tumor Surveillance
- For patients with CDKN1C mutations: consider screening for neuroblastoma with urine catecholamines and chest radiographs 1
- Maintain high clinical suspicion for other reported tumors including rhabdomyosarcoma, pheochromocytoma, and adrenocortical carcinoma 1
Management of Clinical Features
Neonatal Period
- Monitor for hypoglycemia
- Assess for macroglossia and airway management needs
- Evaluate and manage abdominal wall defects (omphalocele/umbilical hernia)
- Screen for visceromegaly (liver, kidney, spleen) 3
Growth Management
- Monitor growth parameters regularly
- Assess for asymmetric growth (hemihyperplasia)
- Note that adult height often exceeds population norms (mean adult height +1.8 SDS) 2
Long-term Follow-up
- Transition to adult care should include education about potential adult manifestations
- Psychosocial support for patients and families
- Genetic counseling for adults with BWS planning families 4
Important Considerations and Pitfalls
Tissue mosaicism: BWS can present with tissue mosaicism, which may lead to false-negative molecular test results. If clinical suspicion remains high despite negative testing, consider testing additional tissue samples 5.
Molecular subtyping importance: Identifying the specific molecular subtype is crucial for determining tumor risk and appropriate surveillance strategies 2.
Surveillance compliance: Emphasize the importance of adhering to the recommended screening schedule, as early tumor detection significantly improves outcomes 1.
Referral to specialists: Management should ideally be coordinated by cancer predisposition specialists familiar with BWS 1.
Evolving guidelines: Surveillance recommendations may evolve as more data becomes available on genotype-phenotype correlations and long-term outcomes 6.