Septo-Optic-Pituitary Dysplasia Is a Clinical Syndrome, Not a Neuropathological Entity: An Autopsy-Based Study

AIMS: To describe neuropathological findings in autopsies of patients with isolated, partial or all classic features of the septo-optic-pituitary dysplasia (SOD) triad, speculate on SOD etiology and ascertain the causes of death. METHOD: Retrospective review of autopsy reports of patients with one or more features of the SOD triad. RESULTS: Twenty-one (14 females) cases were identified. Median age at death was 2.3 years. Two fetuses died soon after birth, and the rest died at postnatal ages of 3 weeks to 50 years. Ten cases had optic nerve hypoplasia (ONH) with either (i) small pituitary gland/hypopituitarism (five cases) or (ii) absent septum pellucidum (SP)/abnormal corpus callosum (CC) (two cases) or (iii) both (three cases). Eleven cases had one or two features of the SOD triad. A wide spectrum of neuropathological findings was evident, with 12 cases resulting from in utero/perinatal vascular lesions in brain regions that led to ONH/chiasm hypoplasia, hypothalamus/pituitary gland anomalies and agenesis or abnormalities in the SP, CC and olfactory bulbs and tracts. Other suspected causes included three genetic (one with holoprosencephaly), two in utero infection and one arachnoid cyst with hydrocephalus. The most common cause of death was a respiratory illness. CONCLUSIONS: The autopsy findings appear to be the result of destructive or less commonly impaired developmental processes. Our findings suggest that SOD is not a single disease entity but represents a syndrome with ONH and one or more of: hypothalamic-pituitary dysfunction and absent SP or abnormal CC. We consider ONH an essential part of SOD.