**6. Midline abnormalities**

*Holoprosencephaly* is a congenital induction disorder, occurring extremely early in pregnancy (3–6 WA), with failing the segmentation of the neural tube [53–57]. This leads to incomplete separation of the prosencephalon. It has been classified into four subtypes: alobar, semilobar, lobar, and a middle interhemispheric fusion variant (syntelencephaly).

The alobar holoprosencephaly is the most severe type, having a complete lack of separation of the cerebral hemispheres; this lead to a single ventricle, absence of the CC and IEF, and fused thalami. In the semilobar type, the cerebral hemispheres are fused anteriorly. In lobar holoprosencephaly, the fusion of the cerebral hemispheres is present at the frontal lobes. The middle interhemispheric fusion variant results from nonseparation of posterior frontal and parietal lobes.

The *corpus callosum* is the largest commissure of the brain, and its development is accelerated between 8 and 20 WA. Any disturbance of this process may lead to CC agenesis or partial agenesis (hypogenesis or dysgenesis). Many CC abnormalities (in terms of dimensions and shape) are frequently diagnosed during pregnancy although their significance is still debated [58–67]. Abnormal CC has been described among patients assessed for mental retardation.

In a similar way, the absence of fluid in the CSP (with or without intact *septum pellucidum* and corpus callosum) may indicate subtle or severe midline brain abnormalities. All these conditions may have significant implications for postnatal neurological development [58, 61, 63–68] (**Figures 24** and **25**).

**Figure 24.** Different cases of holoprosencephaly in the first trimester (a,b). c. a case which associates proboscis.

**Figure 25.** Second-trimester alobar holoprosencephaly (a and b). Short and thick corpus callosum (c).
