Hypothyroidism presents diagnostic challenges when occurring in an extremely unwell infant with hepatoblastoma. This case indicates a possible link between BeckwithWiedemann syndrome (BWS) and severe hypothyroidism.
Antenatally, the baby had polyhydramnios and an abdominal mass. After normal vaginal delivery at 38+4 weeks, examination showed macrosomia (4007 g) small nose, low set ears and inverted V-shaped mouth. Transient hypoglycaemia on day 1 required two glucose boluses, and thereafter resolved. The mass caused abdominal expansion, significant IVC compression and artificial ventilation requirement and Pretext IV hepatoblastoma was diagnosed. Chemotherapy (cisplatin/doxorubicin) was commenced aged 2 weeks but he ultimately required a liver transplant.
At 1 month he developed seizures, paucity of limb movements, abnormal tone and did not fix and follow. EEG showed right sided abnormalities. MRI showed oedema and bilaterally small hippocampi. Array CGH identified a maternally inherited 16p11.2 microduplication (187 kb) most likely of no clinical significance.
Severe hypothyroidism (TSH>100 mU/l, fT4<2.6 pmol/l) was noted at 3 months and thyroxine commenced. Normal Guthrie test was verified and the deterioration in function remains unexplained. Ultrasound showed normal thyroid location and size. No significant iodine exposure had occurred, neither chemotherapeutic agent was known to cause hypothyroidism and he was too young to invoke autoimmunity. Small hippocampi are reported in hypothyroidism, but do not infer aetiology. Hepatoblastoma cannot directly explain onset of hypothyroidism.
The baby died aged 4 months, his course complicated by sepsis, increased ventilation and worsening neurology. Molecular analysis showed significant loss of methylation at ICR2/KvDMR1, confirming a diagnosis of BWS and explaining the hepatoblastoma and hypoglycaemia but not clearly the hypothyroidism.
A tenuous link between BWS and congenital hypothyroidism appears in a small number of reports. Our case is the first reported with non-congenital onset. Additionally, the phenotypic features and severity are atypical for BWS indicating a possible additional genetic mechanism.
12 - 14 Nov 2014
British Society for Paediatric Endocrinology and Diabetes