Beckwith-Wiedemann Syndrome is a complex overgrowth disorder involving genetic and epigenetic changes on chromosome 11p15.5. It affects approximately 1 in 10,340 live births and presents with characteristic features including macrosomia, macroglossia, and abdominal wall defects.

Key Points

• Most common overgrowth syndrome in infancy
• Characterized by prenatal and postnatal overgrowth
• Associated with increased risk of embryonal tumors
• Requires multidisciplinary management approach
• Shows variable expressivity and penetrance

Major Clinical Features

• Macroglossia (Large tongue) - Present in 90% of cases
• Macrosomia (Birth weight >97th percentile)
• Abdominal wall defects (omphalocele, umbilical hernia, diastasis recti)
• Ear creases or pits
• Visceromegaly (particularly kidneys, liver, spleen, pancreas)
• Hemihyperplasia

Minor Features

• Polyhydramnios
• Neonatal hypoglycemia
• Facial nevus flammeus
• Cardiomegaly
• Structural cardiac anomalies
• Advanced bone age
• Characteristic facies (midface hypoplasia, infraorbital creases)

Diagnostic Criteria

Diagnosis requires either:

• ≥3 major criteria, or
• 2 major criteria + 1 minor criterion

Molecular Testing

• Methylation analysis of 11p15
• Chromosomal microarray
• CDKN1C sequencing if indicated

Differential Diagnosis

• Simpson-Golabi-Behmel syndrome
• Perlman syndrome
• Sotos syndrome
• Isolated hemihyperplasia

Management Approach

Neonatal Period

• Monitor blood glucose q4-8h for first week
• Assess feeding difficulties
• Evaluate for omphalocele
• Echocardiogram if indicated

Tumor Surveillance

• Alpha-fetoprotein (AFP) every 3 months until age 4
• Abdominal ultrasound every 3 months until age 8
• Physical exam every 3 months

Long-term Management

• Regular growth monitoring
• Speech therapy for macroglossia
• Orthopedic evaluation for limb length discrepancy
• Developmental assessment
• Genetic counseling

Genetic Basis

Molecular Mechanisms

• Loss of methylation on ICR2 (50% of cases)
• Paternal uniparental disomy (20%)
• Gain of methylation on ICR1 (5%)
• CDKN1C mutations (5%)
• Chromosomal rearrangements (1-2%)

Inheritance

• Usually sporadic (85%)
• Autosomal dominant in some families
• Increased risk with assisted reproductive technology

Prognosis and Complications

Early Complications

• Feeding difficulties
• Respiratory complications from macroglossia
• Hypoglycemia
• Prematurity

Long-term Outcomes

• Normal intelligence in most cases
• 8.6% tumor risk through childhood
• Possible learning disabilities
• Generally good quality of life with appropriate management

Monitoring Requirements

• Regular developmental assessment
• Growth monitoring
• Ongoing tumor surveillance
• Dental and orthodontic care