Determinants of hyperinsulinism severity in children with Beckwith-Wiedemann syndrome

Correlation between 11p15 genotype and hyperinsulinism severity in Beckwith-Wiedemann syndrome

A retrospective cohort of 85 children with Beckwith-Wiedemann syndrome (BWS) and congenital hyperinsulinism (HI) showed significant differences in severity by 11p15 genotype. Patients with paternal uniparental disomy of chromosome 11 (pUPD11) presented more severe HI (max GIR, p=0.004), more frequent diazoxide resistance, and increased surgical risk, particularly when pUPD11 extended into the KATP gene region. Patients with IC2 methylation or CDKN1C variants presented milder forms responsive to diazoxide. A genotype-based clinical management algorithm is proposed.

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This study fills an important gap in BWS management with HI. The proposed genotype-to-treatment algorithm is immediately applicable in multidisciplinary consultation. The correlation between pUPD11 extension into the KATP region and diazoxide resistance is particularly useful for pancreatectomy decision-making.