Endocrine Abstracts

Introduction: Beckwith-Wiedemann syndrome (BWS) is characterized by hyperinsulinaemic hypoglycaemia (HH), overgrowth, tumour predisposition and congenital malformations. Commonly, BWS is caused by epigenetic or genomic alterations, which disrupt genes in one or both of the two imprinted domains on chromosome 11p15.5. Rarely (~1%), paternally inherited duplications of 11p15 can result in BWS phenotype. We describe the first case of BWS associated with a paternally inherited duplication of almost the whole short arm of chromosome 11 and a deletion of the long arm of chromosome 11.

Methods/Results: This patient was born at 34+4 weeks of gestation with birth weight 2850g (91st–98th percentile) by vaginal delivery to Caucasian non-consanguineous parents. In view of macroglossia, micrognathia, right fixed talipes equinovarus and hypotonia, a karyotype was performed. This showed unbalanced female karyotype with duplication of the short arm of chromosome 11[46,XX,rec(11)dup(11p) inv(11)(p12q24.2)] and a deletion of the long arm of chromosome 11. Analysis of parents karyotype revealed father carrying a balanced pericentric inversion of chromosome 11 [(46,XY,inv(11)(p12q24)]. Postnatally she developed HH (blood glucose 2.3 mmol/l, insulin <2 mU/l, free fatty acids 0.15 mmol/l, β-hydroxybutyrate <0.05 mmol/l) and required high intravenous glucose infusion (18 mg/kg per min) to maintain normoglycaemia. She responded well to 5 mg/kg per day of diazoxide. Following Nissen’s fundoplication, her HH was complicated by dumping syndrome. Currently, her blood glucose levels are stable on continuous gastrostomy feeds. She also has problems of developmental delay and obstructive sleep apnea. She is having regular screening with ultrasound of the abdomen and serum tumour markers (AFP, β-hCG).

Conclusion: BWS due to paternally inherited duplications of chromosome 11p15 are rare. Our patient is unique as she has duplication of almost the whole short arm of chromosome 11 and a deletion of the long arm of 11. As she has a chromosomal imbalance larger than usually found in BWS patients, a more severe phenotype is expected.