Beckwith-Wiedemann Syndrome

What is Beckwith-Wiedemann Syndrome?

Beckwith-Wiedemann Syndrome (BWS) is a congenital overgrowth disorder associated with an increased risk of embryonal tumors. The estimated incidence is 1 in 10,000 to 13,700 live births, with most cases occurring sporadically, although familial inheritance has been reported.

Causes

BWS results from epigenetic alterations on chromosome 11p15.5, affecting genes involved in growth regulation, including IGF2 (insulin-like growth factor 2) and CDKN1C. Abnormalities include:

• Loss of imprinting
• Uniparental disomy
• Copy number variations affecting the critical region

Clinical Features

• Macroglossia (enlarged tongue)
• Hemihyperplasia (asymmetric overgrowth of body parts)
• Omphalocele or umbilical hernia
• Neonatal hypoglycemia
• Gigantism or overgrowth in infancy
• Increased risk of embryonal tumors, particularly Wilms tumor and hepatoblastoma

Associated Conditions

• Nephromegaly and renal abnormalities
• Cardiomegaly and congenital heart defects
• Cleft palate or craniofacial anomalies in rare cases

Evaluation and Treatment

• Molecular testing to confirm 11p15.5 alterations
• Abdominal ultrasound and serum AFP screening for tumor surveillance
• Surgical interventions for macroglossia or omphalocele
• Orthopedic monitoring for limb-length discrepancies

Prognosis

With early tumor surveillance and management of overgrowth-related complications, most individuals lead normal lives.

References

1. Mussa A, et al. Clinical spectrum and management of Beckwith-Wiedemann Syndrome. Eur J Pediatr. 2016;175(9):1233-1248.
2. Cohen MM Jr. Beckwith-Wiedemann Syndrome: Historical, clinical, and diagnostic perspectives. Am J Med Genet. 2005;140(19):2388-2394.
3. Brioude F, et al. Expert consensus on Beckwith-Wiedemann Syndrome. J Med Genet. 2018;55(4):205-213.