What is the management approach for Beckwith-Wiedemann syndrome?

Management Approach for Beckwith-Wiedemann Syndrome

Patients with Beckwith-Wiedemann syndrome require regular 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 monitor for Wilms tumor and hepatoblastoma development. 1

Diagnostic Evaluation

• Confirm diagnosis through:

  • Clinical features assessment: macroglossia, omphalocele/umbilical hernia, facial nevus flammeus, hemihyperplasia, and organ overgrowth 1
  • Molecular genetic testing: DNA methylation and copy number variation analysis of chromosome 11p15 region 2
  • Additional testing for patients with negative initial results due to possible tissue mosaicism 2

• Genetic testing should include:

  • Methylation and copy number analysis of chromosome 11p15.5 3
  • Assessment of imprinting control regions (IC1 and IC2) 1
  • Testing for paternal uniparental isodisomy (pUPD11) 1
  • CDKN1C mutation analysis 1

Tumor Surveillance Protocol

Wilms Tumor Screening

• Renal ultrasound every 3 months from birth (or time of diagnosis) through the 7th birthday 1, 3
• More intensive for patients with specific genetic subtypes:
  • IC1 gain of methylation (28% tumor risk) 1
  • pUPD11 (16% tumor risk) 1

Hepatoblastoma Screening

• Full abdominal ultrasound every 3 months from birth 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 (6.7% tumor risk): 1
  • Urine catecholamines and chest radiographs to screen for neuroblastoma

Management of Clinical Features

• Macroglossia: Surgical reduction if causing feeding difficulties, speech problems, or airway obstruction
• Abdominal wall defects: Surgical repair of omphalocele/umbilical hernia
• Neonatal hypoglycemia: Blood glucose monitoring and management
• Hemihyperplasia: Orthopedic monitoring for limb length discrepancies
• Visceromegaly: Regular monitoring of affected organs (liver, kidney, spleen) 4

Genetic Counseling

• Referral to genetics professional for:
  • Determination of recurrence risk for parents 1
  • Testing of relatives when appropriate 1
  • Discussion of inheritance patterns (most cases are not inherited - 85%) 1

Long-term Follow-up

• Monitor for:
  • Renal function
  • Development of secondary malignancies
  • Tumor recurrence
  • Growth and development

Important Clinical Considerations

• Tumor risk varies significantly by molecular subtype: 1

  • IC1 gain of methylation: 28% risk
  • IC2 loss of methylation: 2.6% risk
  • pUPD11: 16% risk
  • CDKN1C mutations: 6.7% risk

• Clinical features associated with higher tumor risk include: 4

  • Visceromegaly affecting three organs (liver, kidney, spleen)
  • Family history with BWS features
  • High birth weight (≥ +2 standard deviations)
  • Diastasis recti

• Surveillance recommendations may differ between US and European centers, with US centers typically recommending uniform screening regardless of molecular subtype 1

• Adults with BWS require ongoing medical follow-up, though specific adult management guidelines have not been well established 5

• Patients should be evaluated and monitored by cancer predisposition specialists whenever possible 1