Clinical Presentation
The proband is a 4-year-old female born large-for-gestational age at 38 weeks to healthy, non-consanguineous Caucasian parents. She was born via spontaneous vaginal delivery complicated by a 3-minute shoulder dystocia with Apgar scores of 4 at 1 minutes, 7 at 5 minutes and 8 at 10 minutes. Birth weight was 4.14 kg (+2.6 SD), length 56cm (+3.68 SD), and head circumference 36.5 cm (+2.7 SD). Pregnancy was remarkable only for a thickened nuchal fold and bilateral choroid plexus cysts on prenatal ultrasound. Amniocentesis was offered, but ultimately declined.
Shortly after birth, she developed mild hypoglycemia with a lowest documented blood glucose of 2.6 mmol/L. Hypoglycemia was treated with a 10% dextrose infusion for the first 24 hours of life, with a maximal glucose infusion rate (GIR) of 4.2 mg/kg/minute. The presence of bilateral proptosis, periorbital edema, subtle left facial hypertrophy, and central hypotonia prompted evaluation for Beckwit-Wiedemann Syndrome (BWS), which returned negative. Newborn metabolic screen was unremarkable, and microarray demonstrated a normal, female result. The hypoglycemia resolved spontaneously and was not investigated further.
At 6 months of age, she presented with a five-minute, generalised tonic-clonic seizure. At presentation, her blood glucose was 1.9 mmol/L and only transiently responsive to two 10% dextrose boluses. A 10% dextrose infusion was started, and she was admitted to hospital for further treatment and investigation. History was significant for several 1–2-minute episodes of ‘staring’ and decreased responsiveness occurring in the preceding two weeks. All episodes occurred in the morning, following periods of fasting overnight. Examination again revealed bilateral proptosis, periorbital edema, and central hypotonia (Figure 1). Auxology demonstrated weight 9.77 kg (+2.1 SD), length 78.3 cm (+5.1 SD), head circumference 46 cm (+2.6 SD).