PURPOSE OF REVIEW: Holoprosencephaly is a disorder of forebrain development 
characterized by a failure of the brain to separate into two hemispheres during 
early development. It is now clear that many cases of holoprosencephaly are 
caused by alterations in the genetic programmes that pattern the nervous system. 
Less is known about how a holoprosencephalic brain either forms or fails to form 
connections between various brain structures.
RECENT FINDINGS: Abnormalities in the corpus callosum, corticospinal tract, 
medial lemniscus and cerebellar peduncles can be seen in holoprosencephaly. 
Diffusion tensor imaging has been and will continue to be an important tool for 
imaging white matter in the brain, and will be reviewed here. Furthermore, 
recent evidence suggests that holoprosencephaly can be associated with delays or 
abnormalities in myelination. The functional implications of white matter 
abnormalities in children with holoprosencephaly is only beginning to be 
understood.
SUMMARY: Modern neuroimaging has led to a better appreciation of the variability 
seen in holoprosencephaly, an anomaly known to have multiple etiologies. Recent 
reviews of the biology of holoprosencephaly identify the condition as a defect 
in dorsoventral patterning. More detailed white and grey matter 
structure-function studies are likely to shed light on how a brain with 
drastically altered composition and connectivity does or does not organize 
itself to accomplish increasingly complex developmental functions.