Introduction: Beckwith-Wiedemann syndrome (BWS) is a multisystem imprinting disorder. Approximately 50% of patients with BWS develop congenital hyperinsulinism (CHI). In this report, we describe the main clinical features in a group of patients with BWS and CHI.
Study: Clinical and laboratory data was collected from all patients with BWS under the care of endocrine units at Alder Hey Childrens Hospital (Liverpool, UK) and Endocrine Research Centre (Moscow, Russia). The group included 12 children (8 males) with BWS and CHI. Median age is 1 year 5 months (range: 3 months 11 years 8 months). All patients were under the follow up of multidisciplinary team and received require surveillance once every 3 months. Common clinical features of BWS included macroglossia (91%), large birth weight for gestational age (66%), ear crease/pit (58%) and umbilical hernia (58%). Methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis in 10 out of 12 children. In 3 patients methylation abnormality of 11p15.5 region was not found. Hence the diagnosis of BWS was made based on clinical features. Seven patients had genetically confirmed BWS (6 patients had ICR2 hypomethylation and 1 patient had mosaic paternal isodisomy of 11p15.5 region). All BWS patients were sporadic in origin. One patient with paternal uniparental isodisomy of 11p15 had two histologically proven embryonic tumors (hepatoblastoma and Wilms tumor) in the infantile period. All patients had presented with recurrent hypoglycemic episodes with elevated plasma concentration of insulin during hypoglycaemia confirming CHI (median insulin level was 66 pmol/l; range: 20.5251). Diazoxide was effective in 10/12 patients (one patient was treated with octreotide and the data from the other patient was not available). The median dose of diazoxide was 6.9 mg/kg/day (range: 310 mg/kg/day). The median duration of diazoxide therapy was 8 months (range: 3 months to 11 years 8 months) and 7 patients are still on treatment.
Conclusion: The majority of BWS patients with CHI were responsive to diazoxide. One patient with mosaic paternal UPD of 11p15 [considered as high risk for tumour] developed Wilms tumour and hepatoblastoma in the infantile period. Genetic analysis would be helpful for disease prognosis in patients with BWS.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology