1. Prechordal Mesoderm

• migrates forward into the area anterior to the notochord during the third week of fetal development where it is necessary for:
  • the development of the midface (anlage of the facial bones)
  • an inductive role in the morphogenesis of the forebrain
• a prechordal mesoderm defect therefore results in:
  • a deficit in the development of the midface
  • induction failure -> incomplete morphogenesis of forebrain
    • failure of embryonic forebrain to cleave (holosphere):
      • sagittally into symmetric cerebral hemispheres -> single lobe telencephalon
      • transverely into the telencephalon & diencephalon
      • horizontally into the olfactory and optic bulbs
      • separate ventricles -> single large ventricle
• defect is:
  • time specific - must occur before 23 weeks gestation
  • stimulus nonspecific - see risk factors above
  • categorized into 3 types (DeMyer 1971):
    • alobar - severe (F>M 3:1)
    • semilobar - moderate
    • lobar - mild (F=M)
  • considered the most devastating of the anterior midline defects
  • the degree of facial malformation is usually predictive of brain malformation ("The face predicts the brain")

1. Alobar Holoprosencephaly

• anophthalmia, cyclopia
• median & bilateral cleft lip and palate
• microcephaly
• severe mental deficiency
• apneic spells, seizures, death

2. Semilobar Holoprosencephaly

• orbital hypotelorism, microphthalmia, coloboma
• normal lip and palate -> absence of philtrum -> median cleft lip
• flat nose -> single-nostril nose (absence of nasal septum)
• mild to severely mentally retarded

3. Lobar Holoprosencephaly

• normal face
• single maxillary incisor
• minimal handicap -> mild to severely mentally retarded

4. Complications

1. Imaging Studies

1. Supportive

• seizures
• hormonal deficiencies

2. Genetic Counselling

• recurrence risk
  • 6% for sporadic, nonchromosomal holoprosencephaly
  • in families with holoprosencephaly in 2 generations:
    • 23% risk of holoprosencephaly in 1st degree relatives

3. Prognosis

• most die before 6 months of age
• mildly affected may live to adulthood

Webpath - U. of Utah - CNS Pathology
The Carter Centers for Brain Research