Hyperinsulinism and Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome first described by Beckwith in 1963.1 The incidence of BWS is about 1:13 700 births, with an equal sex distribution.2 It is a clinically and genetically heterogeneous disorder. Table 1 outlines the major clinical features. The existence of milder forms of BWS probably underestimates this incidence.1 Developmental delay in BWS has been associated with chromosomal duplication, prematurity, and hypoglycaemia.3 The long term survival in BWS is favourable1, although surveillance for tumours is required.4 The phenotype of BWS is likely to result from an imbalance of a number of critical genes at chromosome 11p15. At this location, genetic imprinting with the loss of maternally expressed tumour and/or growth suppressor genes—for example, p57^KIP2and H19—or duplications and unipaternal disomy of paternally expressed growth promoter genes—for example, insulin-like growth factor II—have been implicated in BWS.2 In BWS, 85% of cases are sporadic and 15% are autosomal dominant.2 Identified causes of autosomal dominant BWS include p57^KIP2 mutations and 11p15 duplications and translocations.2 About 30% of the sporadic cases result from p57^KIP2 mutations, unipaternal disomy, or 11p15 duplications and translocations, while 70% have no identified cytogenetic or DNA abnormality.2