Overgrowth syndromes are genetic conditions characterized by a generalized or localized increase in tissue.

Beckwith-Wiedemann Syndrome (BWS)

  • Pathophysiology: Imprinting defect on chr 11p15.5 (maternal methylation loss, paternal UPD) deregulation of imprinted growth genes (IGF2, CDKN1C) somatic overgrowth.
  • Clinical Features:
    • Macrosomia & hemihyperplasia (asymmetric limb/body growth).
    • Macroglossia (leads to airway obstruction and feeding difficulty).
    • Omphalocele or umbilical hernia.
    • Neonatal hypoglycemia (islet-cell hyperplasia hyperinsulinism).
    • Earlobe creases, posterior helical pits, visceromegaly.
  • Diagnosis:
    • Initial: Clinical presentation + blood glucose monitoring.
    • Confirmatory: Genetic testing (methylation analysis/MLPA of 11p15.5).
  • Management:
    • Hypoglycemia: Immediate feeds; IV D10W if refractory.
    • Surgical: Omphalocele repair, reduction glossectomy (if airway/speech compromised).
    • Tumor Surveillance:
      • Abdominal US every 3 months until age 7 (screens for Wilms tumor and hepatoblastoma). c
      • Serum AFP every 3 months until age 4 (screens for hepatoblastoma).
  • Key Differentials:
    • Sotos syndrome: Overgrowth with macrocephaly, intellectual disability, long face; no hypoglycemia.
    • Congenital hypothyroidism: Macroglossia and umbilical hernia; differentiated by lethargy, hypotonia, and ↑ TSH.