Middle interhemispheric variant of holoprosencephaly: a very mild clinical case

Middle interhemispheric variant (MIH) of holoprosencephaly or syntelencephaly was described in 19931 as a fourth subtype of holoprosencephaly (HPE), in addition to the three classic types of alobar, semilobar, and lobar HPE.2 MIH consists of an abnormal midline continuity of the posterior frontal and parietal regions of the cerebral hemispheres, with separation of the basal forebrain, anterior frontal lobes, and occipital regions. Although MIH and classic HPE share a number of similarities, they are related to different embryologic mechanisms. Classic HPE is caused by a defect in the formation of the embryonic floor plate, whereas MIH is secondary to a disturbance of formation of the roof plate.3 The ZIC2 gene plays a critical role in differentiation of the roof plate of the developing embryo in the dorsal midline of the neural tube.3 In mice, decreased levels of ZIC2 result in the failure to form midline CNS structures. In humans, mutations in the ZIC2 gene have been found in ∼3 to 4% of HPE cases, including individuals with MIH, confirming that MIH is a variant of HPE.4 …