Hydrolethalus: a midline malformation syndrome with optic nerve coloboma and hypoplasia

Ophthalmic pathological findings of hydrolethalus, a midline malformation syndrome, were determined in three fetuses aborted between the 14th and 19th gestational week. The eyes were serially sectioned and analyzed using light microscopy and a panel of 13 antibodies to neuronal, glial, epithelial, and mesenchymal elements of the eye. The general morphological and antigenic development of the anterior segment, retina and choroid were normal, but some lens fibers were vacuolated and irregular in all eyes. A coloboma of the optic nerve was constant and corresponded in its severity to the systemic manifestations. It ranged from segmental dysplasia of the optic nerve head to a colobomatous orbital cyst with secondary microphthalmos and deranged development of the eye. Glial tissue extended through a defect in the sheaths of the optic nerve in three eyes, communicating with retinoblastic tissue in the orbit. Evidence of secondary optic nerve hypoplasia was present in all eyes, and a separate chorioretinal coloboma was present in one eye. Ocular anomalies should be considered one hallmark of hydrolethalus syndrome, and they may help to differentiate it from other overlapping malformation syndromes. In particular, colobomatous dysplasia and hypoplasia of the optic nerve seem to be typical of hydrolethalus syndrome. Histopathological studies of the eyes may help the neuropathologist in making the differential diagnosis of midline malformation syndromes.