Background
Septo-optic dysplasia (SOD) is a heterogeneous congenital condition. The aim of this study was to investigate the clinical phenotypes of a large cohort of children with SOD, Multiple Pituitary Hormone Deficiency (MPHD) and Optic Nerve Hypoplasia (ONH), with a focus on endocrine testing.
Methods
Retrospective single-centre longitudinal study of children with SOD (n:171), MPHD (n:53) and ONH (n:35). SOD+ and SOD- indicate patients with or without hypopituitarism, respectively.
Findings
All deficits were more frequent and occurred earlier in MPHD than SOD+ [Hazard Ratios (HR): 0·63(0·45,0·89) for GH, 0·48(0·34,0·69) for TSH, 0·55(0·38,0·80) for ACTH, 0·28(0·11,0·68) for gonadotropins], except Diabetes Insipidus (DI) [HR: 2·27(0·88,5·9)]. Severe hypothalamo-pituitary (H-P) abnormalities were more frequent in MPHD [80·0% vs 41·6%, p<0·0001 for Ectopic Posterior Pituitary (EPP)]. Stalk and PP abnormalities were associated with more severe endocrine phenotypes and placed a subgroup of SOD+ at risk of developing deficits earlier. SOD and ONH shared heterogeneous phenotypes ranging from pubertal delay to precocity and from leanness to extreme obesity, whilst MPHD had GnD and obesity only. Mortality was recorded in 4·2% (6/144) SOD and 3·2% (1/31) ONH, and only in patients with multisystem phenotypes.
Interpretation
More than a single disease, SOD represents a spectrum of malformative conditions involving different brain structures and characterised by a dynamic and sequential nature of endocrine. In contrast, MPHD displays a more homogeneous phenotype of (mainly) anterior pituitary early-onset failure. Stalk and PP abnormalities place a subgroup of SOD+ at a higher risk of early-onset deficits. Additionally, there are striking differences between the SOD and MPHD cohorts in terms of pubertal progression. The shared phenotypes between ONH and SOD could be partly explained by common hypothalamic dysfunction. The differences between the cohorts are important as they may aid in planning management and preventing morbidity by dictating earlier interventions
