ESPE Abstracts

Introduction: Rubenstein-Taybi Syndrome (RSTS)is a rare multiple congenital anomaly syndrome with a prevalence of 1:100,000 to 1:125,000. It is classically characterized by postnatal growth deficiency, microcephaly, learning difficulties, increased risk of tumour formation, broad thumbs and halluces and dysmorphic facial features including highly arched eyebrows, long eyelashes, downslanting palpebral fissures, broad nasal bridge, beaked nose, high arched palate and characteristic grimacing or abnormal smile. The majority of cases are caused by haploinsufficiency of the CREBBP gene. However, variants disrupting the paralogous gene, EP300, are found in up to 10% of patients. An expanding phenotype for RSTS is being recognised. Hyperinsulinaemic hypoglycaemia (HH) has been identified as a novel association, and there have been two case reports of HH in patients with RSTS in the literature so far. Here, we present two further patients with RSTS and HH.

Case reports: Patient 1 was born at 38-weeks gestation with a birth weight of 2.60 Kg. She had mild dysmorphic features, bilateral choanal atresia requiring nasal stent insertion in the neonatal period, gastro-oesophageal reflux disease, unsafe swallow and developmental delay. A gastrostomy was inserted at 18 months. She had persistent episodes of hypoglycaemia and was diagnosed with HH at 1.54 years. Genetic testing was negative for mutations in known genes causing HH and imaging showed diffuse uptake of 18F-DOPA on PET scan. The HH was unresponsive to diazoxide, octreotide and nifedipine. She was subsequently started on sirolimus therapy and demonstrated a good response. She was eventually diagnosed with RSTS, due to a truncating mutation in the EP300 gene, at 2.38 years following genetic testing as part of the Deciphering Developmental Disorders (DDD) study. Patient 2 was diagnosed with RSTS (heterozygous mutation c.1044delT in CREBBP) in the neonatal period with typical facial appearance, broad and angulated thumbs, broad halluces and undescended testes. He was found to have persistent post-prandial HH and was started on diazoxide at 38 days. Diazoxide was stopped and he had a Nissens fundoplication and gastrostomy insertion at 0.77 years. Following gastrostomy insertion he was started on continuous feeds. He was subsequently diagnosed with dumping syndrome at 4.38 years and was started on acarbose with feeds.

Conclusion: A number of conditions involving histone modification such as RSTS and Kabuki syndrome are associated with hyperinsulinism. Additional cases are needed to confirm the association between RSTS and HH, particularly in EP300 mutations which have a wider phenotypic spectrum.