PPM - Beckwith-Wiedemann Syndrome and Spectrum-Description and References

Description and References

Pdf Summary

Beckwith-Wiedemann Syndrome (BWS) and its spectrum are genetic conditions characterized by overgrowth, macroglossia, abdominal wall defects, and a risk for embryonal tumors. Specific traits include lateralized overgrowth, organomegaly, renal anomalies, and skin features. BWS is primarily caused by genetic or epigenetic alterations in the 11p15.5 chromosomal region and occurs in approximately 1 in 10,340 live births. While a molecular cause is detected in about 80% of cases, geneticists should consider BWS within a spectrum that includes isolated lateralized overgrowth.<br /><br />Initial evaluations should focus on confirming a diagnosis using a scoring system that assesses cardinal and suggestive features; a score of 4 confirms classical BWS. Molecular tests, particularly methylation analysis of the IC1 and IC2 domains, are critical for diagnosis. Further testing may require CDKN1C sequencing or cytogenetic analysis, especially when initial tests yield incomplete results. When these tests don't confirm BWS, clinicians should consider other related genetic syndromes.<br /><br />Management involves genetic counseling about the risk of embryonal tumors and recurrence risk within families, notably up to 10-15% familial cases, with a recurrence risk possibly reaching 50%. Assisted reproductive technologies increase BWSp risk four to six times.<br /><br />For monitoring, a tumor screening protocol includes regular abdominal and renal ultrasounds, and potentially measuring serum alpha-fetoprotein, despite some international debates about its necessity. The most common tumors in children with BWSp are Wilms tumor, hepatoblastoma, and neuroblastoma, with specific screening protocols suggested based on genetic findings.<br /><br />Clinicians must ensure appropriate diagnostic and management strategies, including genetic counseling to navigate this complex spectrum of overgrowth conditions. Policies may vary slightly based on the latest genotype findings, emphasizing the importance of updated international consensus guidelines for managing BWSp.

Keywords

Beckwith-Wiedemann Syndrome

genetic conditions

overgrowth

macroglossia

embryonal tumors

chromosomal region 11p15.5

molecular diagnosis

genetic counseling

tumor screening

international guidelines