Abstract
BackgroundBeckwith–Wiedemann syndrome (BWS) is an overgrowth syndrome with variable clinical phenotype and complex molecular aetiology. It is mainly caused by dysregulation of the chromosome 11p15 imprinted region, which results in overgrowth in multiple tissues, often in a mosaic manner.Case presentationA large-for-gestational-age infant without any other somatic features of BWS presented with medically refractory hyperinsulinism (HI) requiring 80% pancreatectomy. Next generation sequencing with congenital HI sequencing panel identified a pathogenic ABCC8:c.1792C > T (p.Arg598Ter) variant of paternal origin, suggestive of focal HI. However, pancreatic histology revealed atypical findings of coalescing nests and trabeculae of adenomatosis scattered with islets with isolated enlarged, hyperchromatic nuclei scattered throughout the pancreas. Methylation analysis, SNP-based chromosomal microarray and short tandem repeat markers analysis revealed mosaic segmental paternal uniparental disomy (UPD) 11p15.5-p15.1 in the pancreatic tissue, but not the peripheral blood, suggestive of BWS/BW-spectrum HI.ConclusionsThis case highlights the importance of integrating the clinical presentation and subsequent clinical course, together with radiological, genetic and histological findings in the definitive diagnosis of this rare yet clinically important entity. In addition, this is the first report that demonstrated the level of paternal inherited c.1792 T pathogenic variant in the pancreatic tissue being directly correlated to the mosaic level of pUPD.
Highlights
Beckwith–Wiedemann syndrome (BWS) is an overgrowth syndrome with variable clinical phenotype and complex molecular aetiology
We report a case of a large-for-gestational-age infant with medically refractory HI due to a paternally transmitted KATP mutation, who was subsequently diagnosed with mosaic BWS related to mosaic segmental pUPD 11 based on molecular testing of the pancreatic lesion
We described an infant with severe HI resulting from a paternally-inherited ABCC8 mutation in conjunction with mosaic segmental pUPD11p15 demonstrated in the pancreatic tissue from the second resection but not in peripheral blood leucocytes, suggestive of BWS/BWspectrum HI
Summary
This case highlights the importance of integrating the clinical presentation and subsequent clinical course, together with radiological, genetic and histological findings in the definitive diagnosis of this rare yet clinically important entity.
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