ESPE Abstracts

Background: Septo-optic dysplasia (SOD) is a highly heterogeneous condition with a variable phenotype, defined as two or more features of the classical triad: i) optic nerve hypoplasia, ii) midline brain defects, and iii) pituitary hormone abnormalities.

Objective and hypotheses: To describe the clinical, endocrine, and neuroimaging features in eight children with SOD.

Method: Eight (six males) consecutive patients, diagnosed with SOD in a Regional Paediatric Endocrinology Service, underwent a retrospective review of all clinical, biochemical, neuroimaging, and genetic characteristics.

Results: All children met the SOD diagnostic criteria: 50% had all three features and 50% two out of three. SOD was diagnosed in the neonatal period in 5/8 (62.5%) patients. Maternal age was <25 years in 4/8 (50%) cases. Midline brain defects were identified in 7/8 (87.5%) patients, with schizencephaly in 57%. Hypoplastic optic nerves and chiasm was described in 6/8 (75%) patients. Pituitary MRI scanning revealed abnormal gland in 50% of the cases. Clinically the most prevalent features were moderate/severe visual impairment and developmental delay (62.5%), endocrine disorders (62.5%), and seizures (62.5%). Three cases (37.5%) developed hydrocephalus, with acute onset in 2/3, requiring urgent VP shunt insertion and resulting in a fatal outcome in one child. All five patients with endocrinopathies had GH deficiency (one with panhypopytuitarism). Growth was normal in the absence of endocrine dysfunction (3/7), and with GH therapy 2/5 patients experienced normal height velocity (−0.97 to 1.14 SDS) and normal BMI. Karyotype was normal in all cases and screening for HESX1, PROKR2, FGFR1, FGF8, LHX4, and SOX2 mutations was negative.

Conclusion: This case series confirms that the phenotypic heterogeneity in SOD is high. Genetic screening was negative, in keeping with previous data. The acute complication of sudden onset hydrocephalus is novel and has not been described to date. These complex patients with a life threatening condition require careful clinical management.