Clinical and molecular diagnosis, screening and management of Beckwith–Wiedemann syndrome: an international consensus statement

Abstract

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.

Hyperinsulinaemic hypoglycaemia in deoxyguanosine kinase deficiency

“…Hypoglycaemia screen during one of these episodes confirmed HH ( 9 Although poor insulin clearance due to liver failure is a possible mechanism of HH in DGUOK deficiency, literature suggests that hypoglycaemia often precedes significant liver dysfunction (and as also was the case in our patient) and hence unlikely to be the underlying cause. On this feeding regimen, frequent episodes of hypoglycaemia were observed.…”

Two Consecutive Pregnancies with Simpson-Golabi-Behmel Syndrome Type 1: Case Report and Review of Published Prenatal Cases

“…Other major features are organomegaly (53%), neonatal hypoglycaemia (51%), facial naevus flammeus (52%), and ear creases/pits (63%). The incidence of polyhydramnios is 53% [Brioude et al, 2018].…”

“…BWS is unlikely to present skeletal and cardiac anomalies, except cardiomegaly [Knopp et al, 2015]. Therefore, in suspicious cases of fetal overgrowth with congenital anomalies, GPC3 gene sequencing would be insufficient; genomic investigations should include BWS testing [Brioude et al, 2018].…”

DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2‐DMR0 as a DNA methylation‐dependent, P0 promoter‐specific enhancer

“…15 As suggested by these findings, genome-wide DNA methylation analysis in SoS patients with NSD1 defects showed hypomethylation at thousands of CpG sites. [19][20][21] BWS is caused by dysregulation of imprinted genes within the IGF2/H19 or CDKN1C/KCNQ1OT1 imprinted domains at 11p15. 18 BWS is an imprinting disorder characterized by overgrowth, macroglossia, abdominal wall defects, and predisposition to embryonal tumors.…”