White matter maturation in holoprosencephaly (HPE) was assessed by MRI scans in 47 patients (age 1 day to 16 years, median age 7 months) evaluated at the University of California, San Francisco. White matter maturation was delayed in 25 of 47 patients, and was easier to detect in infants compared to older children (24/32 affected <1 year of age, 1/15 >1 year of age). The classic severe subtypes of HPE were especially involved (2/4 lobar, 20/31 semilobar, 3/6 alobar), whereas 0/6 with MIH had myelin delay. The classic and MIH variants of HPE appear to have different patterns of myelination, reflecting different underlying causes. [1]

COMMENT. Infants with classic holoprosencephaly (HPE) have delayed white matter maturation. HPE results from abnormal development of the floor plate and ventral neural tube, at the level of the prosencephalon, and oligodendrocytes, involved in myelin production, originate in the ventral aspect of the neural tube close to the floor plate. These processes depend on induction by the protein sonic hedgehog (SHH), which is mutated in some forms of familial HPE (Roessler E et al, 1996, cited by Barkovich, 2002). The finding of normal myelination in MIH supports the theory of a normal floor plate in this subtype of HPE, and separate genetic and environmental factors in etiology.