Background: Beckwith-Wiedemann syndrome (BWS) characterised by a group of clinical abnormalities (macrosomia, macroglossia, neonatal hypoglycaemia, omphalocoele and umbilical hernia) results from dysregulation of imprinted genes due to mosaic paternal uniparental isodisomy (patUPD) of 11p15.5. Its association with tumours of embryonic origin is well documented and screening guidelines largely aim to detect hepatoblastoma and Wilms tumours during the first decade of life. BWS features have been noted in 2530% of infants with placental mesenchymal dysplasia (PMD), a distinct condition with cystic placental histology and mosaicism for genome-wide patUPD. One previous case of bilateral phaeochromocytoma has been reported in PMD.
Case presentation: We describe the case of a 12 year old female diagnosed with PMD in infancy on the basis of cystic placental histology, BWS-like clinical features and confirmatory genetic analyses. Her early years were complicated by severe congenital hyperinsulinism requiring subtotal pancreatectomy and hepatoblastoma. Antenatal sonography at 18, 22, and 28 weeks gestation documented bilateral cystic adrenomegaly which had regressed on postnatal imaging by 5 months of age. During prolonged screening a unilateral asymptomatic right sided adrenal cystic lesion was noted at age 11 which demonstrated no appreciable uptake on targeted imaging but which had increased in size over 12 months of surveillance to 3.7×3.1×3.6 cm and was secretory of noradrenaline and dopamine; this was confirmed as a phaeochromocytoma after an uneventful surgical removal of the lesion. Regular surveillance for a recurrent or left sided lesion is ongoing.
Conclusion: BWS and PMD share clinical and genetic features and an increased risk of malignancy. Their association with phaeochromocytoma, while rare, may not be co-incidental given that there is a known association between these tumours and maternal loss of 11p15 genes. Due consideration of continued screening for phaeochromocytomas beyond the first decade of life may be appropriate for individuals with PMD.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology