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

Abstract

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.

Visually impaired children with posterior ocular malformations: pre‐ and neonatal data and visual functions

“…Optic nerve hypoplasia (ONH) and optic nerve/fundus coloboma are common posterior ocular malformations in Swedish children with visual impairment (Blohmé & Tornqvist 1997a). Although ONH and coloboma are usually considered as separate clinical entities, they have been described as occurring in the same child (Hotchkiss & Green 1979; Slamovits et al 1989; Kivela et al 1996) (Filous et al 1998; Pecorella et al 2002) and it has been suggested that together they represent a spectrum of optic nerve abnormalities caused by an early insult to closely related embryonic structures (Brown 1982). ONH, thought to occur through an adverse prenatal advent affecting the anterior visual pathway (Frisen & Holmegaard 1978), may occur in isolation or with central nervous system (CNS) abnormalities and/or life‐threatening endocrinological insufficiencies (Brodsky & Glasier 1993; Brodsky et al 1997).…”