BeckwithWiedemann syndrome (BWS) is an overgrowth syndrome caused by multiple epigenetic and genetic changes. It is due to genetic and epigenetic mechanisms affecting the balance of imprinted genes on chromosome 11p15.5. This region has two imprinted control regions, ICR1 and ICR2. ICR1 contains the genes H19 and IGF2 genes with H19 being maternally expressed and IGF2 paternally expressed. ICR2 contains the KCNQ1, KCNQ1OT1, and CDKN1C genes. Hypomethylation of KvDMR1 (an intronic CpG island within the KCNQ1 gene) on the maternal allele is the most common (about 50%) genetic abnormality observed in patients with BWS. Hyperinsulinaemic hypoglycaemia (HH) is one of the most common biochemical abnormalities observed in patients with BWS. The frequency of HH in patients with BWS varies between 30 and 50% and usually resolves spontaneously but a small group (<5%) may require a partial/total pancreatectomy. The mechanism/s of HH in patients with BWS is/are unclear. The aim of our study was to assess the clinical presentation of HH in patients with BWS due specifically to KvDMR1 hypomethylation. We identified 19 patients with BWS due to KvDMR1 hypomethylation. In this group of patients ten had no HH, five had mild transient (days) HH which resolved spontaneously, and four required diazoxide therapy. None of the patients in this series required pancreatectomy for the HH. Diazoxide was stopped after 6 months in those patients who were commenced on this treatment. Apart from the differences in the presentation of HH these patients also showed marked clinical heterogeneity with respect to the other features of BWS. Macroglossia was the most frequently observed feature with seventeen out of nineteen patients positive for this finding but there was no correlation between extent of macroglossia and severity of HH. Our observations suggest that in patients with BWS due to hypomethylation of the KvDMR1 locus the presentation of HH can be variable, from having no HH to requiring diazoxide therapy. Although the patient numbers are small, HH requiring a pancreatectomy seems to be rare in this group of patients. Further studies are required to understand why patients with BWS due to KvDMR1hypomethylation show marked heterogeneity in the clinical presentation of HH.
09 - 11 Nov 2011
British Society for Paediatric Endocrinology and Diabetes