Endocrine Abstracts

Introduction: Beckwith-Wiedemann Syndrome (BWS), a genetic imprinting disorder linked to 11p15, showcases overgrowth traits, including macrosomia, macroglossia, and abdominal wall defects. Characterized by specific genotype-phenotype correlations and recognized as a cancer predisposition syndrome (nephroblastoma, hepatoblastoma, neuroblastoma and adrenocortical carcinoma), our four case reports provide insights into varied clinical presentations.

Case reports: Case 1: a 1-year and 4-month-old boy conceived through in vitro fertilization was diagnosed with BWS at 11 months. MLPA detected maternal hypomethylation (11p15-IC2). Notable physical features include macroglossia and a forehead flat hemangioma. Literature supports a 10-fold BWS risk with assisted-reproduction-technology, potentially indicating milder phenotype (Carli D et al, 22). Case 2: We examine a 2-year and 6-month-old girl with suspected BWS identified prenatally due to macroglossia, omphalocele, and polyhydramnios. At 1-day old, she underwent surgical intervention for omphalocele. BWS was confirmed at 6 months through MLPA, revealing the same submolecular type as in case 1 (IC2-LoM). Case 3: We introduce a 2-year and 7-month-old girl. Neonatally, the phenotypic features, with macroglossia, transient hypoglycemia and ear lobe creases raised suspicion of BWS. By 1 year and 6 months, she had surgical reduction for macroglossia, and, over time, the diastasis of the rectus abdominis resolved spontaneously. At 2 years, an orthopedic exam revealed a leg length discrepancy, suggesting shoe lift usage. The patient’s clinical score is 7 points, exceeding the diagnostic threshold for BWS without molecular confirmation (Brioude et al., 18). Case 4: a 1-year and 3-month-old girl presented with neonatal hypoglycemia and hyperinsulinism (elevated insulin and C-peptide levels). Central adrenal insufficiency (low cortisol, lower normal range ACTH) was treated with hydrocortisone. An early ultrasound revealed a left adrenal tumor that later resolved, likely due to adrenal hemorrhage. Genetic tests, including WES and MLPA, showed no evidence of congenital hyperinsulinism or BWS-associated deletions/duplications. Like case 3, the clinical score is 7 points (including macroglossia, ear pits), negating a need for molecular confirmation. Repeated suprarenal ultrasound demonstrated no tumor formations on both sides. In all four cases, the tumor screening consists of serum alpha-fetoprotein (AFP) levels and abdominal ultrasound every three months, were within normal limits. IC2-LoM, found in 2 of our cases is associated with the lowest tumor risk, being the most frequent.

Conclusion: Given the complex genetics and diverse phenotypes associated with BWS, a multidisciplinary team approach is essential. This collaborative effort aims to coordinate various aspects of care throughout childhood, particularly highlighting the need for tumor surveillance.