Introduction: Beckwith-Wiedemann Syndrome (BWS) is a rare genetic disorder that could be associated with embryonal tumours. Genotype based categorisation of patients enables better screening strategies. We present a patient with BWS who developed atypical congenital hepatoblastoma and atypical Wilms tumour in infancy.
Case Report: A 2 day old infant was referred with recurrent hypoglycaemia and high intravenous glucose requirement [>12 mg/kg/min]. He was born at 36 weeks gestation by an elective LSCS, being large for gestational age. A hypoglycaemia screen confirmed congenital hyperinsulinism (CHI) [blood glucose 1.6 mmol/L, plasma insulin 97 pmol/L, c-peptide 523 pmol/L, free fatty acids <176 umol/L and B-hydroxybutyrate <23 umol/L]. Following unresponsiveness to maximum dose of diazoxide [15 mg/kg/day], he was commenced on subcutaneous octreotide with a good response [22 mg/kg/day]. He was subsequently switched to once monthly Lanreotide injections. Genetic analysis for ABCC8 and KCNJ11 were negative. He was noted to have features of BWS [macroglossia, hepatomegaly and single earlobe crease]. Genetic analysis revealed hypomethylation at KCNQ1OT1:TSS-DMR and hypermethylation at the H19/IGF2:IG-DMR consistent with mosaic paternal isodisomy of the 11p15 region without copy number changes. Screening ultrasound on day 4 of life revealed bilateral renal enlargement and a focal mass in the left lobe of liver, the biopsy of which revealed hepatoblastoma showing exclusively epithelial component. He was resistant to chemotherapy. He underwent ultrasound guided resection as the tumour was not readily identifiable and the histology was more consistent with hepatocellular carcinoma. MRI abdomen at 3 months of age revealed a lesion in left kidney suggestive of Wilms Tumour that was confirmed on biopsy [Immunohistochemistry was positive for CD56 and WT1]. He was started on induction chemotherapy with Vincristine and Actinomycin D but showed no response. Post-nephrectomy histology at 5 months of age revealed mixed type, intermediate risk, stage 3 disease. In view of the poor response to initial chemotherapy, treatment was changed to Cyclophosphamide with Doxorubicin and Carboplatin with Etoposide. He is planned for post-operative radiotherapy.
Conclusion: We report, for the first time, a rare association of atypical hepatoblastoma and atypical Wilms tumour in an infant with BWS, who also had diazoxide resistant CHI. Patients with BWS, should be screened for embryonal tumours as early as possible. Early onset tumours may show more atypical features and be resistant to chemotherapy.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology