MIDLINE CEREBRAL DYSGENESIS, DYSFUNCTION OF THE HYPOTHALAMIC-PITUITARY AXIS, AND FETAL ALCOHOL EFFECTS

Objective.-Neuropathologic evaluation was performed on an infant with fetal alcohol effects. Design.-Coronal brain sections and representati ve tissue blocks stained with hematoxylin-eosin, silver stain, and imm unocytochemical stains for hypothalamic and pituitary hormones were ev aluated for neuropathologic abnormalities. Patient.-A 2.5-month-old Am erican Indian girl who had been exposed to first-trimester maternal bi nge alcohol abuse died after persistent problems of growth failure, so dium imbalance, aberrant temperature regulation, respiratory distress, and seizures. Results.-Autopsy revealed severe microcephaly, hypertel orism, midfacial hypoplasia, a high-arched palate, shortened palpebral fissures, and a small brain. The frontal lobes were fused anteriorly; olfactory bulbs and tracts were absent; and optic nerves were hypopla stic. An enlarged and bulbous hypothalamus obscured the pituitary glan d. The thalamus and caudate nuclei were fused across the midline. Post eriorly, the single ventricle split to form rudimentary lateral horns. The anterior corpus callosum, septum pellucidum, fimbria, and fornice s could not be identified. The anterior commissure and supraoptic nucl ei were microscopically present. Many Purkinje cells were horizontally positioned, with abnormal dendritic structure. The posterior pituitar y lobe was absent, and the infundibulum was flanked by a hypoplastic a denohypophysis and a large subarachnoid heterotopia. Immunocytochemica l studies identified only vasopressin and neurophysin in the hypothala mus and only growth hormone and prolactin in the pituitary gland. Conc lusion.-To our knowledge, an association between fetal alcohol effects and a complex cerebral anomaly with features of incomplete holoprosen cephaly and septo-optic dysplasia has not previously been reported and suggests a possible common pathogenesis needing further study.