Holoprosencephaly in an 8.5-week triploidy gestation

Abstract

Holoprosencephaly (HPE), the most common malformation of the human forebrain, is because of failed midline cleavage of the developing forebrain between the 18th and 28th days of gestation. HPE occurs in up to one in 250 gestations, though less than 3% of these survive to birth (Matsunaga and Shiota, 1977; Leoncini et al., 2008). Severity is defined by the extent of brain malformations; categories include alobar (the most severe type), semilobar, and lobar HPE (Plawner et al., 2002). The spectrum of facial dysmorphisms is wide, but at the severe end of the spectrum, individuals may show cyclopia or synophthalmia (fusion of the optic vesicles with incomplete eye development), a proboscis (a tubular nasal appendage above the fused eyes), and severe microcephaly. HPE may occur as one feature in a syndrome (as in Smith-Lemli-Opitz syndrome) (Kelley et al., 1996), result from teratogenic influences (such as the use of cholesterol lowering agents in early gestation) (Edison and Muenke, 2004), or be because of mutations in genes involved in forebrain development (such as SHH) (Muenke and Beachy, 2000). Most often, HPE occurs in the context of cytogenetic anomalies. Up to 50% of patients born with HPE have cytogenetic anomalies; an even greater proportion of fetuses with HPE have cytogenetic anomalies (Muenke and Beachy, 2000).