Holoprosencephaly: A medical condition with devastating consequences

At early stages human embryological development, the neural tube begins a process called ventral induction. During ventral induction, the neural tube divides the tube into 3 primary brain vesicles, or subdivisions, that later differentiate into 5 vesicles (Figure 1) . Between the 18th and the 28th day of gestation, the anterior portion of the neural tube, the prosencephalon, divides into two parts (telencephalon and diencephalon - Figure 1). These parts then undergo a cleavage process followed by inward rotation (Figure 2). Under normal circumstances, this would result in a telencephalon and diencephalon divided into two halves each. Incomplete cleavage and failure of rotation of the prosencephalon results in a brain malformation known as holoprosencephaly (Figure 2). Holoprosencephaly is a spectrum of conditions with symptoms varying from mild to severe. In the most severe form, alobar holoprosencephaly, the telencephalon and diencephalon are fused and a single ventricle is formed. In semilobar holoprosencephaly, the diencephalon remains fused but the telencephalon presents a fissure posteriorly. In lobar holoprosencephaly the diencephalon may or may not be fused, but the telencephalon presents a nearly normal fissure. Individuals with the alobar form experience severe mental retardation and seizures that are difficult to treat. The condition is frequently associated with facial malformations (i.e. malformations of the nose, lips and eyes, or in extreme cases cyclopia - fused eyes) and in many cases is fatal due to severe brain malformations. The other two forms result in limited clinical deficits such as cognitive delay and seizures that can be treated; life expectancy in these individuals is not reduced.

Figure 1: Embryological development of the brain vesicles. Attribution: Tauiris, CC ASA 3.0

Figure 2: Normal ventral induction process and holoprosencephaly. Attribution: Dutra drawing