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Almost four decades have passed since William DeMeyer linked facial dysmorphism and holoprosencephaly (HPE) with the phrase, “the face predicts the brain.” HPE is a congenital brain malformation in which the hemispheres and basal ganglia are incompletely separated to varying degrees.1 Subsequent advances in neuroimaging and molecular biology permit accurate anatomic and, in many cases, molecular classification of children with HPE.
HPE is the most common brain malformation in humans, with a prevalence of 1:250 in early embryogenesis2 and 1.26:10,000 in a prospective birth cohort study.3 In the normal 7- and 8-week fetus, the telencephalic vesicles, precursors of the hemispheres, expand more rapidly than the dorsal midline roof plate. Low levels of proliferation and high rates of apoptosis in the roof plate lead to fixation and relative invagination of this midline structure and consequent separation of the growing …
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