Fetal growth patterns in Beckwith-Wiedemann syndrome

Area of Science:

• Genetics
• Developmental Biology
• Pediatrics

Background:

• Beckwith-Wiedemann syndrome (BWS) is a complex overgrowth disorder with diverse molecular etiologies.
• Understanding fetal growth variations among BWS subtypes is crucial for diagnosis and management.

Purpose of the Study:

• To investigate and compare fetal growth patterns across four distinct molecular subtypes of Beckwith-Wiedemann syndrome.
• To correlate growth differences with specific molecular mechanisms and clinical manifestations.

Main Methods:

• Observational study comparing gestational age and neonatal growth parameters in 247 BWS patients.
• Utilized gestational age-corrected standard deviation scores (SDS) and proportionality indexes.
• Analyzed data stratified by molecular subtypes: IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation.

Main Results:

• Significant differences in fetal growth patterns were observed among the four molecular subtypes.
• IC1-GoM cases presented with higher weight and length, indicating extreme macrosomia and disproportion.
• IC2-LoM and CDKN1C mutation subgroups showed increased prematurity rates and more proportionate growth.
• UPD cases displayed growth patterns intermediate between IC1-GoM and IC2-LoM, with body mass disproportion similar to IC1-GoM.

Conclusions:

• Fetal growth patterns in BWS are distinct and directly influenced by underlying molecular mechanisms.
• The observed growth variations highlight the heterogeneity of BWS and inform clinical expectations for different subtypes.
• These findings underscore the importance of molecular subtyping for understanding BWS pathogenesis and patient outcomes.