Holoprosencephaly

Excerpt

Holoprosencephaly (HPE) results from an incomplete midline cleavage of the forebrain (prosencephalon). It includes a wide spectrum of intracranial and craniofacial midline defects and a myriad of clinical manifestations, consisting of neurologic impairment and dysmorphism of the brain and face. It is the most common malformation of forebrain development. Evidence suggests that HPE can be present either sporadically or can have a syndromic association. The defect associated with HPE occurs at approximately 3 to 4 weeks post-conception (between day 18 and day 28 of embryonic life) and is a disorder of gastrulation.

The HPE phenotype continuum has been divided into 3 categories by DeMyer and Zeman and modified by DeMyer. These categories include:

Alobar: This is the most severe and most common form (two-thirds of all HPE cases), characterized by a complete failure to partition the forebrain into the left and right hemispheres; this results in a single, centrally located ventricle.

Semilobar: Partial forebrain cleavage

Lobar: Almost complete forebrain cleavage

Middle interhemispheric variant (syntelencephaly): A rare variant with an abnormal midline union of the posterior frontal and parietal lobes.

Septo-preoptic variant: This rarest variant is mild, and the midline fusion is restricted to the telencephalon's septal or preoptic region.