Recent advances in neonatal Beckwith-Wiedemann syndrome: from molecular diagnosis to multidisciplinary management-a narrative review.

BACKGROUND AND

OBJECTIVE

Beckwith-Wiedemann syndrome (BWS) is a complex congenital overgrowth disorder resulting from genetic and epigenetic dysregulation at the 11p15.5 locus. It is clinically characterized by macrosomia, macroglossia, abdominal wall defects (e.g., omphalocele), refractory hypoglycemia, and an increased risk of embryonal tumors such as Wilms tumor (WT) and hepatoblastoma (HB). This review aims to synthesize recent advances in the molecular diagnosis, neonatal clinical management, and long-term surveillance of BWS, with the goal of providing evidence-based, multidisciplinary strategies to improve outcomes.

METHODS

This is a narrative review based on current literature and clinical guidelines. We integrated findings from recent studies on molecular diagnostics (including methylation-specific testing and uniparental disomy analysis), neonatal interventions, tumor surveillance protocols, and multidisciplinary care models for BWS.

KEY CONTENT AND FINDINGS: Molecular subtyping now enables precise diagnosis and tumor risk stratification, guiding personalized care. In the neonatal period, critical issues such as hypoglycemia due to hyperinsulinism and airway compromise from macroglossia require specialized interventions [e.g., continuous glucose monitoring (CGM) and tongue-reduction surgery]. Meanwhile, omphalocele is addressed following standard surgical management approaches. Long-term care emphasizes structured tumor screening [abdominal ultrasound and serum alpha-fetoprotein (AFP)], growth and developmental monitoring, functional rehabilitation, and genetic counseling to address familial recurrence risks.

CONCLUSIONS

The integration of molecular diagnostics with coordinated, multidisciplinary management significantly enhances early detection, acute care, and long-term outcomes in neonates with BWS. Future efforts should focus on refining risk-adapted screening protocols and advancing precision medicine approaches to further optimize care and quality of life for affected individuals.